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1.
Inflammopharmacology ; 28(5): 1141-1152, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32797326

RESUMO

The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Ibuprofeno/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Infecções por Coronavirus/complicações , Humanos , Ibuprofeno/efeitos adversos , Inflamação/etiologia , Inflamação/prevenção & controle , NF-kappa B/efeitos dos fármacos , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral/complicações
2.
PLoS One ; 15(8): e0237017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756588

RESUMO

Procyandin A2 (PCA2) is a polyphenolic compound which is isolated from grape seeds. It has been reported that PCA2 exhibits antioxidative and anti-inflammatory effects, but its molecular mechanism is still poorly understood. This study tests the hypothesis that PCA2 suppresses lipopolysaccharide (LPS)-induced inflammation and oxidative stress through targeting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and NF-E2-related factor 2 (Nrf2) pathways in RAW264.7 cells. PCA2 (20, 40, 80 µM) exhibited no significant cytotoxicity in RAW264.7 cells and showed an inhibitory effect on an LPS-induced nitrite level. Pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and reactive oxygen species (ROS) were suppressed by PCA2 with a concentration range of 0-80 µM. The mRNA levels of TNF-α and IL-6 were inhibited by PCA2 (80 µM). The hallmark-protein expression of the NF-κB (p-IKKα/ß, p-IκBα, and p-p65) and MAPK (p-p38, p-JNK, and p-ERK) pathways were decreased by PCA2 in LPS-stimulated RAW264.7 cells. In addition, immunofluorescence results indicated that PCA2 (80 µM) promoted the translocation of NF-κB/p65 from the cytoplasm into the nucleus. PCA2 upregulated the expressions of Nrf2 and HO-1 and downregulated the expression of Keap-1. Simultaneously, PCA2 (80 µM) reversed LPS-induced Nrf2 translocation from the nucleus into the cytoplasm. Collectively, PCA2 protect cells against the damage from inflammation and oxidative injury, which suggest a potential therapeutic strategy for inflammatory and oxidative stress through targeting NF-κB, MAPK, and Nrf2 pathways in RAW264.7 cells.


Assuntos
Catequina/metabolismo , Catequina/farmacologia , Inflamação/tratamento farmacológico , Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Heme Oxigenase-1/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
3.
Toxicol Lett ; 333: 130-139, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32763311

RESUMO

Trichloroethylene (TCE) is a widely used industrial solvent that causes trichloroethylene hypersensitivity syndrome (THS) with multi-system damage, including kidney injury. Clinical studies have shown that the complement system is important for TCE-induced kidney injury. Our previous study found excessive deposition of complement C3, mainly on the glomerulus, indicating that local renal complement is activated after TCE sensitisation. However, whether local renal complement activation mediates TCE-induced immune kidney injury and the underlying mechanisms remain unknown. Therefore, we established a TCE percutaneous sensitisation BALB/c mouse model to explore the mechanisms by pretreating with or without the complement activation antagonist, cathepsin L inhibitor (CatLi). As expected, more C3 and C3a were detected mainly on glomerulus of TCE positive sensitisation (TCE+) mice. Renal dysfunction and pathological damage were also clearly observed in TCE+ mice. Moreover, the mRNA and protein expression of ET-1 increased significantly with local renal complement activation after TCE sensitisation, leading to cytokines release and inflammation. In addition, activation of p38MAPK and NF-κBp65 pathways were detected in kidneys of TCE+ mice, and CatLi pretreatment decreased these changes through complement activation antagonisation. Our research uncovered a novel role of local renal complement activation during immune kidney injury after TCE sensitisation through induction of ET-1 signalling and inflammation.


Assuntos
Ativação do Complemento/imunologia , Endotelina-1/metabolismo , Hipersensibilidade/metabolismo , Rim/efeitos dos fármacos , Insuficiência Renal/metabolismo , Tricloroetileno/toxicidade , Animais , Ativação do Complemento/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Hipersensibilidade/imunologia , Inflamação , Rim/imunologia , Rim/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/efeitos dos fármacos , NF-kappa B/imunologia , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/imunologia , Transdução de Sinais
4.
Acta Cir Bras ; 35(5): e202000502, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32638843

RESUMO

PURPOSE: Changrui enema, a traditional Chinese medicine prescription, is used as a supplementary treatment for acute radiation proctitis (ARP). Herein we explored the inhibition effects of Changrui enema on NF-κB and VEGF in ARP mice. METHODS: A total of 120 C57BL/6 mice were divided randomly into normal mice group, ARP mice group, western medicine enema group (dexamethasone combined with gentamicin), and Changrui enema group. ARP mice were established by pelvic local irradiation. The expression of IL-1ß, NF-κB, VEGF, AQP1, AQP3, p-ERK1/2 and p-JNK was determined by immunohistochemistry or western blot. RESULTS: The study firstly found that Changrui enema alleviated ARP mice. The expression of IL-1ß, NF-κB, VEGF, AQP1 and p-ERK1/2 was increased in ARP mice, and was reserved by Changrui enema. However, the expression of AQP3 and p-JNK was decreased in ARP mice, and was up-regulated by Changrui enema. CONCLUSIONS: Changrui enema is an effective treatment with fewer side effects for ARP. The mechanism of Changrui enema may be related to the inhibition of inflammation-induced angiogenesis. Changrui enema inhibits IL-1ß and NF-κB expression as well as VEGF expression. Interestingly, AQP1 promotes angiogenesis, while AQP3 inhibits inflammation. Changrui enema probably inhibits AQP1 expression by down-regulating p-ERK1/2, and improves AQP3 expression by up-regulating p-JNK.


Assuntos
Medicamentos de Ervas Chinesas , NF-kappa B , Proctite , Lesões por Radiação , Fator A de Crescimento do Endotélio Vascular , Animais , Medicamentos de Ervas Chinesas/farmacologia , Enema , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , Proctite/tratamento farmacológico , Proctite/etiologia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
5.
Gene ; 753: 144819, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32485309

RESUMO

Vitamin D is one of the indispensable nutrients of human body. When vitamin D is deficient, it can cause a series of related diseases, such as respiratory tract infection. The regulatory role of vitamin D in inflammatory immune response and defense has attracted more and more attention. However, few studies have shown that vitamin D regulates inflammation and autophagy in Aspergillus fumigatus infected lungs. In this study, we will explain the mechanism of vitamin D regulating inflammation and autophagy in Aspergillus fumigatus infected lungs. METHODS: Different concentrations of Aspergillus fumigatus spores were injected into mice with deficien diets (VitD-) or sufficient vitamin D (VitD + ) , and the survival rates were recorded. Then, the weight changes of rats were measured every other time. At the same time, a gauze was used to filter the lapped lung tissue to get the pulmonary spores and measured the amount of the spores. The mice with the same concentration of Aspergillus fumigatus infected were cut off and the lung tissue for pathological examination in the deficien diets (VitD-) group or sufficient vitamin D (VitD + ) group. Moreover, the expression of inflammation related factors TNF-α, IL-1ß, IL-6 in lung was measured by immunohistochemical method. The expression of TNF-α, IL-1ß, IL-6 in the serum of vitamin D deficiency and sufficient mice were measured by ELISA. In vitro, we obtained macrophages from healthy mice and mixed cultures of Aspergillus fumigatus spores and lung macrophages in medium with or without vitamin D. After the cells were infected with Aspergillus fumigatus spores, the expressions of NF-κB and IL-8 were detected by RT-PCR and Western blot. The RAW264.7 cells transfected with GFP-LC3BII were mixed with Aspergillus fumigatus spores, and the expression of cell fluorescence was observed by the fluorescence microscope with or without chloroquine and rapamycin , and the autophagy flow of the cells was measured by Western blot. In the RAW264.7 cells, Lentivirus transfection and SiRNA technologies were used to enhance or reduce the expression of the NF-κB gene (siNF-κB) for investgating the influence of high or low expression of NF-κB in the autophagic flow of vitamin D + or vitamin D-treated RAW264.7 cells. RESULTS: The survival rate of vitamin D deficient mice infected Aspergillus fumigatus was significantly lower than that of vitamin D sufficient mice, while the number of spores, spore activity, pathological changes of lungs and inflammation in the lungs of vitamin D deficient mice were more severe than that of vitamin D sufficient mice. In vitro cell experiments, when cell was stimulated with vitamin D, the expressions of NF-κB and IL-8 in cells were lower. The autophagic flux and TNF-α, IL-1ß, IL-6 and LC3BII in vitamin D group were significantly lower than those in vitamin D deficiency group. CONCLUSIONS: Vitamin D deficiency can aggravate the inflammatory damage in the lungs of Aspergillus fumigatus. When the body is sufficient in vitamin D, if the lungs infect Aspergillus fumigatus spores, the body may resist the infection of Aspergillus fumigatus by reducing the expression of NF-κB, inflammatory factors and autophagy.


Assuntos
Autofagia/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Vitamina D/metabolismo , Animais , Aspergilose/imunologia , Aspergilose/metabolismo , Aspergillus fumigatus/imunologia , Aspergillus fumigatus/patogenicidade , Aspergillus fumigatus/fisiologia , Citocinas/genética , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Macrófagos/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo , Deficiência de Vitamina D/metabolismo
6.
Arch Med Res ; 51(6): 524-534, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32473749

RESUMO

OBJECTIVE: To investigate the effects and molecular mechanism of melatonin (MT) on NF-κB and TGF-ß/Smad3 signaling pathways in db/db diabetic mice. METHODS: db/db diabetic mice were divided into five groups treated with melatonin at doses of 50, 100, 200 µg/kg, the urinary concentration was detected by ELISA, renal histology was observed in PAS paining. Mouse mesangial cells were divided into mannitol control group, normal control group, normal control + MT group, high glucose group, high glucose + different concentrations (10, 100, 1000) µmol/L MT group. The proliferation of mesangial cells was detected by EdU kit; the expression of NF-κBp65, ColⅣ and Fn were detected by laser confocal system; the concentrations and mRNA levels of ColⅣ and Fn were detected by ELISA and qRT-PCR. the expressions of ColⅣ, Fn, IκB, p-IκB, TGF-ß1, Smad3 and p-Smad3 were detected by Western blot in renal tissues and mesangial cells. RESULTS: MT treatment could markedly improve the kidney histopathologic lesions. Compared with the db/m mice, 24 h urinary albumin excretion rate (UAER) and the expressions of ColIV, Fn, p-IκB/IκB, NF-κBp65, TGF-ß1 and p-Smad3/Smad3 were decreased after melatonin treatment (p <0.05). Compared with the control group, the proliferation function of mesangial cells in high glucose group was significantly enhanced, and the expressions of ColIV, Fn, p-IκB/IκB, NF-κBp65, TGF-ß1 and p-Smad3/Smad3 in mesangial cells were significantly up-regulated (p <0.05), and these changes were significantly lowered in MT treatment. CONCLUSION: Melatonin can inhibit renal inflammation and fibrosis by inhibiting the NF-κB and TGF-ß1/Smad3 signaling pathways, and melatonin may be a promising therapeutic target in diabetic nephropathy.


Assuntos
Depressores do Sistema Nervoso Central/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Fibrose/tratamento farmacológico , Rim/patologia , Melatonina/uso terapêutico , NF-kappa B/efeitos dos fármacos , Proteína Smad3/efeitos dos fármacos , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Animais , Depressores do Sistema Nervoso Central/farmacologia , Diabetes Mellitus Experimental , Nefropatias Diabéticas/patologia , Masculino , Melatonina/farmacologia , Camundongos , NF-kappa B/antagonistas & inibidores , Proteína Smad3/antagonistas & inibidores , Fator de Crescimento Transformador beta1/antagonistas & inibidores
7.
Braz J Med Biol Res ; 53(6): e8885, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401925

RESUMO

In this study, we aimed to analyze the anti-cancer effects of ß-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of ß-elemene and paclitaxel. The in vitro results showed that ß-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or ß-elemene treatment alone. Results demonstrated that ß-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of ß-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with ß-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that ß-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Sesquiterpenos/administração & dosagem , Animais , Western Blotting , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Transfecção
8.
Braz J Med Biol Res ; 53(6): e9489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401927

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund's adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin(IL)-1ß, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-κB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-κB p65 and p-IκB-α. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-κB pathway. However, the exact target molecules of this pathway need to be determined in further studies.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Citocinas/sangue , Dissacarídeos/administração & dosagem , Flavonoides/administração & dosagem , Adjuvante de Freund/administração & dosagem , Glicosídeos/administração & dosagem , NF-kappa B/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Biomarcadores/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , NF-kappa B/metabolismo , Ratos , Fator de Necrose Tumoral alfa/sangue
9.
Toxicology ; 440: 152487, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418911

RESUMO

Renal toxicity is the primary factor that limits clinical use of cisplatin (CP). A previous study showed that omeprazole (OME) protected against CP-induced toxicity in human renal tubular HK-2 cells and rat kidneys. However, the protective mechanisms of OME have not been characterized. We evaluated the ability of OME to inhibit CP-induced inflammation, and characterized the pathways responsible for this effect. Rats were randomly divided into five groups (n = 10/group). The OME groups were intraperitoneally injected with 1.8 or 3.6 mg OME /kg body weight once daily for 5 days. One hour after final administration of vehicle or OME, all rats (except those in control group and OME alone group) were intraperitoneally injected with 15 mg/kg CP. Twenty-four hours after CP injection, the surgery was applied. The time points and dosing of OME and CP were calculated based on previous studies and the therapeutic dose for patients. Omeprazole attenuated CP-induced apoptosis and damage in vivo and in vitro, as evidenced by increased cell viability and prevention of structural damage. Omeprazole ameliorated CP-induced renal injury through inhibition of NF-κB activation and IκBα degradation, and down-regulation of toll-like receptor 4 (TLR4) and Nod-like receptor protein 3 (NLRP3). Lipopolysaccharide, a TLR4 agonist, was used to verify this mechanism. The results indicated that OME inhibited CP-induced expression of inflammatory proteins, and this effect was blunted by co-treatment with LPS in HK-2 cells. These findings suggested that the protective effects of OME against CP-induced kidney damage may occur through inhibition of the TLR4/NF-κB/NLRP3 signaling pathway. This study provided evidence that OME may be a promising agent to inhibit CP-induced nephrotoxicity.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Antineoplásicos , Cisplatino , NF-kappa B/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Omeprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Proteínas I-kappa B/efeitos dos fármacos , Testes de Função Renal , Masculino , Ratos , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
10.
Biochim Biophys Acta Proteins Proteom ; 1868(6): 140412, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32179183

RESUMO

Matrix metalloproteinases (MMPs) are zinc-dependent extracellular matrix remodeling endopeptidases. MMPs cleave various matrix proteins such as collagen, elastin, gelatin and casein. MMPs are often implicated in pathological processes, such as cancer progression including metastasis. Meanwhile, microorganisms produce various secondary metabolites having unique structures. We designed and synthesized dehydroxymethylepoxyquinomicin (DHMEQ) based on the structure of epoxyquinomicin C derived from Amycolatopsis as an inhibitor of NF-κB. This compound inhibited cancer cell migration and invasion. Since DHMEQ is comparatively unstable in the body, we designed and synthesized a stable DHMEQ analog, SEMBL. SEMBL also inhibited cancer cell migration and invasion. We also looked for inhibitors of cancer cell migration and invasion from microbial culture filtrates. As a result, we isolated a known compound, ketomycin, from Actinomycetes. DHMEQ, SEMBL, and ketomycin are all NF-κB inhibitors, and inhibited the expression of MMPs in the inhibition of cellular migration and invasion. These are all compounds with comparatively low toxicity, and may be useful for the development of anti-metastasis agents.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/antagonistas & inibidores , Cicloexanonas/antagonistas & inibidores , Metaloproteinases da Matriz/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Actinobacteria/metabolismo , Animais , Antineoplásicos/química , Benzamidas/síntese química , Benzamidas/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cicloexanonas/síntese química , Glioxilatos/antagonistas & inibidores , Glioxilatos/metabolismo , Humanos , Metaloproteinase 11 da Matriz/efeitos dos fármacos , Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Modelos Moleculares , Subunidade p50 de NF-kappa B/metabolismo , Invasividade Neoplásica , Neoplasias , Quinonas/química
11.
PLoS One ; 15(3): e0230142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210464

RESUMO

Neuroinflammation is a major risk factor associated with the pathogenesis of neurodegenerative diseases. Conventional non-steroidal anti-inflammatory drugs are prescribed but their long term use is associated with adverse effects. Thus, herbal based medicines are attracting major attraction worldwide as potential therapeutic candidates. Tylophora indica (Burm. f) Merrill is a valuable medicinal plant well known in Ayurvedic practices for its immunomodulatory, anti-oxidant, anti-asthmatic and antirheumatic activities. The present study aimed to elucidate the anti-neuroinflammatory potential of water and hydroalcoholic leaf extracts of micropropagated plants of T. indica using BV-2 microglia activated with lipopolysaccharide as an in vitro model system and development of an efficient reproducible protocol for its in vitro cloning. Non cytotoxic doses of the water and hydroalcoholic extracts (0.2µg/ml and 20µg/ml, respectively) were selected using MTT assay. α-Tubulin, Iba-1 and inflammatory cascade proteins like NFκB, AP1 expression was studied using immunostaining to ascertain the anti-neuroinflammatory potential of these extracts. Further, anti-migratory activity was also analyzed by Wound Scratch Assay. Both extracts effectively attenuated lipopolysaccharide induced microglial activation, migration and the production of nitrite via regulation of the expression of NFκB and AP1 as the possible underlying target molecules. An efficient and reproducible protocol for in vitro cloning of T. indica through multiple shoot proliferation from nodal segments was established on both solid and liquid Murashige and Skoog's (MS) media supplemented with 15µM and 10µM of Benzyl Amino Purine respectively. Regenerated shoots were rooted on both solid and liquid MS media supplemented with Indole-3-butyric acid (5-15µM) and the rooted plantlets were successfully acclimatized and transferred to open field conditions showing 90% survivability. The present study suggests that T. indica may prove to be a potential anti-neuroinflammatory agent and may be further explored as a potential therapeutic candidate for the management of neurodegenerative diseases. Further, the current study will expedite the conservation of T. indica ensuring ample supply of this threatened medicinal plant to fulfill its increasing demand in herbal industry.


Assuntos
Microglia/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Plantas Medicinais/crescimento & desenvolvimento , Tylophora/crescimento & desenvolvimento , Complexo 1 de Proteínas Adaptadoras/efeitos dos fármacos , Complexo 1 de Proteínas Adaptadoras/metabolismo , Linhagem Celular , Humanos , Técnicas In Vitro , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Microglia/imunologia , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico
12.
Phytother Res ; 34(8): 2074-2081, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32189385

RESUMO

The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM-induced increase in calcified nodule formation and osteogenesis-specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF-κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM-directed therapeutics for CAVD.


Assuntos
Estenose da Valva Aórtica/prevenção & controle , Valva Aórtica/patologia , Calcinose/prevenção & controle , Curcumina/química , Curcumina/uso terapêutico , NF-kappa B/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Valva Aórtica/efeitos dos fármacos , Curcumina/farmacologia , Cardiopatias Congênitas , Doenças das Valvas Cardíacas , Humanos
13.
Toxicol Appl Pharmacol ; 391: 114919, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32045587

RESUMO

Ulcerative Colitis is a universal autoimmune disease with high incidence rates worldwide. It is characterized by the existence of many other concurrent immune-associated ailments, including diabetes. The used strategies for the management of this highly costing and complicated disease face great challenges. Therefore, the urge for new medication with fewer side effects and high efficacy is growing. The peroxisome proliferator-activated receptor-gamma (PPARγ) and nuclear factor Kappa-B (NF-κB) can be considered as crucial targets for the treatment of ulcerative colitis. Several studies reported the antioxidants, anti-inflammatory, and antiapoptotic actions of gliclazide and evaluated its cardioprotective and renoprotective effects. However, its impact on ulcerative colitis has never been investigated. This study delineated the effect of gliclazide administration on ulcerative colitis induced by acetic acid in rats and the underlying molecular mechanisms. Gliclazide (10 mg/kg; p.o) prominently decreased colon tissue injury as assessed by the histopathological analysis as well as myeloperoxidase, and intercellular adhesion molecule-1 levels. Gliclazide significantly alleviated the proinflammatory mediator, IL-6, promoted the anti-inflammatory cytokine, IL-10 and, withheld oxidative stress in the injured colon tissues. The protective effect of gliclazide was mediated through the upregulation of PPARγ and downregulation of NF-κB expression. The diminution of ulcerative colitis was also accompanied by an inhibition of the elevated activity and expression of mitogen-activated protein kinases and caspase-3 as assessed by Western blot and immunohistochemistry, respectively. Our findings spotlight, for the first time, the potential of the antidiabetic agent, gliclazide, to attenuate the experimentally induced ulcerative colitis. Therefore, gliclazide might be a propitious agent for the management of ulcerative colitis in diabetic patients.


Assuntos
Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Gliclazida/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ácido Acético , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Inibidores de Caspase/farmacologia , Colite Ulcerativa/patologia , Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Masculino , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/efeitos dos fármacos , Peroxidase/biossíntese , Peroxidase/genética , Ratos , Ratos Wistar
14.
Acta Biochim Biophys Sin (Shanghai) ; 52(2): 180-191, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31990036

RESUMO

Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.


Assuntos
Proteínas de Ligação a DNA/antagonistas & inibidores , Células Endoteliais/patologia , MicroRNAs/farmacologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Antioxidantes/farmacologia , Dioxigenases/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana , Humanos , MicroRNAs/genética , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transfecção
15.
Toxicol Lett ; 319: 49-57, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693926

RESUMO

Blast lung injury is associated with high morbidity and mortality. Vaporized perfluorocarbon (PFC) inhalation has been reported to attenuate acute respiratory distress syndrome in humans and animal models. However, the effect of vaporized PFC on blast lung injury is still unknown. In this study, we investigated the protective effects and potential underlying mechanisms of action of vaporized PFC on blast lung injury in a canine model. This was a prospective, controlled, animal study in adult male hybrid dogs randomized to sham, blast (B), blast plus mechanical ventilation (B + M), and blast plus PFC (B + P) groups. All groups except for the sham were exposed to blast wave. The B + P group was treated with vaporized PFC for 1.5 h followed by 5.5 h mechanical ventilation. B + M group received 7.5 h mechanical ventilation and B group was observed for 7.5 h. Blast lung injury was induced using a shock tube. Blood gas, inflammatory cytokines, and oxidative stress were measured. Expression of nuclear factor (NF)-κB activation, mitogen-activated protein kinase (MAPK) and nuclear factor, erythroid 2 like 2 (Nrf2) were measured using western blot. Lung injury observed after blast exposure was marked by increased histopathological scores, ratio of lung wet to dry weight. PFC treatment attenuated blast lung injury as indicated by histopathological scores and ratio of lung wet to dry weight. PFC treatment downregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), and upregulated superoxide dismutase (SOD) activity. PFC also suppressed expression of MAPK/NF-κB and Nrf2 protein levels. Our results suggest that PFC attenuated blast-induced acute lung injury by inhibiting MAPK/NF-κB activation and inducing Nrf2 expression in dogs.


Assuntos
Traumatismos por Explosões/tratamento farmacológico , Fluorcarbonetos/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Administração por Inalação , Animais , Traumatismos por Explosões/patologia , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Cães , Fluorcarbonetos/administração & dosagem , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos
16.
Crit Care Med ; 48(1): e40-e47, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634234

RESUMO

OBJECTIVES: The knowledge that agmatine is found in the human body has existed for several years; however, its role in sepsis has not yet been studied. In the present study, we investigate the role of agmatine in the progression and treatment of sepsis. DESIGN: Clinical/laboratory investigations. SETTING: Medical centers/University-based research laboratory. SUBJECTS: Elective ICU patients with severe sepsis and healthy volunteers; C57BL/6 mice weighing 18-22 g. INTERVENTIONS: Serum agmatine level and its associations with inflammatory markers were assessed in patients with sepsis. Agmatine was administered intraperitoneally to mice before a lipopolysaccharide challenge. Human peripheral blood mononuclear cells and murine macrophages were pretreated with agmatine followed by lipopolysaccharide stimulation. MEASUREMENTS AND MAIN RESULTS: Serum agmatine levels were significantly decreased in patients with sepsis and lipopolysaccharide-induced mice, and correlated with Acute Physiology and Chronic Health Evaluation II score, procalcitonin, tumor necrosis factor-α, and interleukin-6 levels. In a therapeutic experiment, exogenous agmatine attenuated the cytokine production of peripheral blood mononuclear cells from patients with sepsis and healthy controls. Agmatine also exerted a significant beneficial effect in the inflammatory response and organ damage and reduced the death rate in lipopolysaccharide-induced mice. Imidazoline I2 receptor agonist 2-benzofuran-2-yl blocked the pharmacological action of agmatine; whereas, other imidazoline receptor ligands did not. Furthermore, agmatine significantly impaired the inflammatory response by inactivating nuclear factor-κB, but not protein 38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and inducible nitric oxide synthase signaling in macrophages. Activation of imidazoline I2 receptor or knockdown of ribosomal S6 kinase 2 counteracted the effects of agmatine on phosphorylation and degradation of inhibitor of nuclear factor-κBα. CONCLUSIONS: Endogenous agmatine metabolism correlated with the progression of sepsis. Supplemental exogenous agmatine could ameliorate the lipopolysaccharide-induced systemic inflammatory responses and multiple organ injuries through the imidazoline I2 receptor-ribosomal S6 kinase 2-nuclear factor-κB pathway. Agmatine could be used as both a clinical biomarker and a promising pharmaconutrient in patients with severe sepsis.


Assuntos
Agmatina/uso terapêutico , Receptores de Imidazolinas/fisiologia , NF-kappa B/fisiologia , Proteínas Quinases S6 Ribossômicas 90-kDa/fisiologia , Sepse/tratamento farmacológico , Transdução de Sinais/fisiologia , Agmatina/farmacologia , Animais , Células Cultivadas , Progressão da Doença , Humanos , Receptores de Imidazolinas/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 90-kDa/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
17.
Acta Cir Bras ; 34(11): e201901104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31859817

RESUMO

PURPOSE: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. METHODS: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. RESULTS: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1ß, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. CONCLUSION: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.


Assuntos
Cardiotônicos/farmacologia , Genisteína/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , NF-kappa B/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Aspartato Aminotransferases/sangue , Western Blotting , Creatina Quinase/sangue , Citocinas/sangue , Lactato Desidrogenases/sangue , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-31878134

RESUMO

Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.


Assuntos
Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Modelos Animais , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos
19.
J Appl Oral Sci ; 27: e20180713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31691738

RESUMO

Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. OBJECTIVE: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. METHODOLOGY: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. RESULTS: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1ß (IL-1ß) and IL-6 protein expression. CONCLUSIONS: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Calcitriol/farmacologia , NF-kappa B/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Perda do Osso Alveolar , Animais , Western Blotting , Conservadores da Densidade Óssea/análise , Calcitriol/análise , Caspase 1/análise , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Gengiva/patologia , Imuno-Histoquímica , Interleucina-1beta/análise , Interleucina-6/análise , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/análise , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Periodontite/patologia , Porphyromonas gingivalis , Receptores de Hidrocarboneto Arílico/análise , Valores de Referência , Reprodutibilidade dos Testes , Resultado do Tratamento
20.
BMC Oral Health ; 19(1): 236, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684930

RESUMO

BACKGROUND: Antiinflammatory effect of 1,25-dihydroxyvitamin D3 (1,25D3) has been reported in periodontitis, but the exact mechanisms remain unclear. Oral epithelial cells are recently highlighted as an important regulator of inflammation in this disease. This in vitro study was established to investigate the effect of 1,25D3 on key proinflammatory cytokine IL-6 production and aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB) signaling in oral epithelial cells upon the stimulation of lipopolysaccharide (LPS) from periodontal pathogens. METHODS: OKF6/TERT-2 oral keratinocytes were incubated with LPS and different concentrations of 1,25D3, and levels of IL-6 production were determined using enzyme-linked immunosorbent assay (ELISA). Expression of vitamin D receptor (VDR), and activation of AhR was examined using western blot analysis, and phosphorylation of NF-κB was detected using cell-based protein phosphorylation ELISA. RESULTS: 1,25D3 inhibited LPS-induced IL-6 overexpression in OKF6/TERT-2 cells. Additionally, 1,25D3 increased VDR expression and AhR activation, and repressed NF-κB phosphorylation. Furthermore, 1,25D3 suppressed IL-6 expression and enhanced VDR expression and regulated AhR/NF-κB signaling activation in a dose-dependent manner after 48 h treatment. CONCLUSIONS: These results suggest that 1,25D3 may inhibit LPS-induced IL-6 overexpression in human oral epithelial cells through AhR/NF-κB signaling. Our findings may provide an explanation for the antiinflammatory effect and therapeutic benefit of 1,25D3 in periodontitis.


Assuntos
Colecalciferol/administração & dosagem , Células Epiteliais , Interleucina-6/metabolismo , Interleucina-8/metabolismo , NF-kappa B/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico , Vitamina D/análogos & derivados , Humanos , Interleucina-6/genética , Interleucina-8/genética , Lipopolissacarídeos/administração & dosagem , Vitamina D/farmacologia
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