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1.
Medicine (Baltimore) ; 98(30): e16610, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348308

RESUMO

The purpose of this study was to investigate the influences of varied anesthetic methods and depths on inflammatory cytokines and stress hormone levels in radical operation among colon cancer patients during perioperative period.A total of 120 patients were collected in the study and randomly divided into 4 groups, A: general anesthesia + Narcotrend D1, B: general anesthesia + Narcotrend D2, C: general anesthesia + epidural anesthesia + Narcotrend D1, D: general anesthesia + epidural anesthesia + Narcotrend D2. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, cortisol (Cor), adrenocorticotropic hormone (ACTH), and endothelin-1 (ET-1) were measured adopting commercial kits before anesthesia (T0), 4 hours after surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3).There was no significant difference in basic clinical characteristics among the groups. In comparison with group A, B and C, group D showed significantly lower levels of TNF-α, IL-6, IL-10, Cor, ACTH, and ET-1 at T1 and T2 (all, P < .05). Significantly higher levels of TNF-α, IL-6, IL-10, Cor, and ACTH were detected at T1 and T2 than those at T0 (all, P < .05), whereas, at T3, the levels of inflammatory cytokines and stress hormones were all decreased near to preoperation ones.General anesthesia combined with epidural anesthesia at Narcotrend D2 depth plays an important role in reducing immune and stress response in patients with colon cancer from surgery to 24 hours after surgery.


Assuntos
Anestesia Epidural/métodos , Anestesia Geral/métodos , Neoplasias do Colo/cirurgia , Citocinas/biossíntese , Mediadores da Inflamação/metabolismo , Hormônio Adrenocorticotrópico/biossíntese , Citocinas/sangue , Quimioterapia Combinada , Endotelina-1/biossíntese , Feminino , Humanos , Hidrocortisona/biossíntese , Mediadores da Inflamação/sangue , Interleucinas/biossíntese , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese
2.
Arch Virol ; 164(10): 2451-2458, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273469

RESUMO

Avian reovirus (ARV) is a member of the genus Orthoreovirus in the family Reoviridae and causes a severe syndrome including viral arthritis that leads to considerable losses in the poultry industry. Innate immunity plays a significant role in host defense against ARV. Here, we explored the interaction between ARV and the host innate immune system by measuring mRNA expression levels of several genes associated with the MDA5 signaling pathway. The results showed that expression peaks for MDA5, MAVS, TRAF3, TRAF6, IRF7, IKKɛ, TBK1 and NF-κB occurred at 3 days postinfection (dpi). Moreover, type I IFN (IFN-α, IFN-ß) and IL-12 expression levels peaked at 3 dpi, while type II IFN (IFN-γ), IL-6, IL-17 and IL-18 expression reached a maximum level at 1 dpi. IL-8 changed at 5 dpi, and IL-1ß and TNF-α changed at 7 dpi. Interestingly, several key IFN-stimulated genes (ISGs), including IFITM1, IFITM2, IFITM5, Mx1 and OASL, were simultaneously upregulated and reached maximum values at 3 dpi. These data indicate that the MDA5 signaling pathway and innate immune cytokines were induced after ARV infection, which would contribute to the ARV-host interaction, especially at the early infection stage.


Assuntos
Helicase IFIH1 Induzida por Interferon/biossíntese , Linfócitos/patologia , Orthoreovirus Aviário/crescimento & desenvolvimento , Doenças das Aves Domésticas/patologia , Infecções por Reoviridae/veterinária , Transdução de Sinais , Transcriptoma , Animais , Galinhas , Citocinas/biossíntese , Interações Hospedeiro-Patógeno , Imunidade Inata
3.
Artigo em Chinês | MEDLINE | ID: mdl-31262112

RESUMO

Objective: To explore the effect of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin (TSLP) in nasal mucosa of allergic rhinitis (AR) rats. Methods: One hundred Wistar rats,half male and half female,were randomly divided into 5 groups by random number table method: control group, AR model group,budesonide group,18ß-sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg groups, with 20 rats in each group. AR animal models were established by ovalbumin (OVA) sensitization in the other four experimental groups. After successful modeling, budesonide and 18ß-sodium glycyrrhetinic acid were given in each group,and the detection time points were 2 weeks and 4 weeks. The distribution of TSLP in rat nasal mucosa was detected by immunohistochemistry,and the expression of TSLP in rat nasal mucosa was determined by Western blot at the protein level. The expression of TSLP-mRNA in rat nasal mucosa was detected and compared by real-time fluorescence quantitative PCR (RT-PCR) at mRNA level. The concentrations of IL-4 and OVA-sIgE in rat serum were measured and compared by ELISA. One-way analysis of variance and the least significant difference method were used for the comparison among groups, LSD t test was used for the comparison between the two groups,and the difference was statistically significant (P<0.05). Results: Immunohistochemistry confirmed existence of TSLP in rat nasal mucosa, especially in epithelial cells,endothelial cells and epithelial cilia. Western blot and RT-PCR suggested that the expression of TSLP and TSLP-mRNA in nasal mucosa of AR model group was significantly higher than that of control group (2 weeks TSLP: 1.795 9±0.131 4 vs 0.990 5±0.164 2, 4 weeks TSLP: 1.809 7±0.253 4 vs 0.870 3±0.124 4; 2 weeks TSLP-mRNA:4.582 9±0.697 7 vs 1.108 7±0.081 1, 4 weeks TSLP-mRNA:4.814 4±0.662 8 vs 1.001 0±0.155 3; all P<0.05). After 2 weeks and 4 weeks of drug intervention,the expression of TSLP and TSLP-mRNA was inhibited in nasal mucosa of budesonide group,18ß-sodium sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg group,which was significantly different from that of AR model group (2 weeks TSLP: (0.897 8±0.081 8)/(1.072 1±0.113 6)/(1.396 6±0.133 9) vs 1.795 9±0.131 4; 4 weeks TSLP: (1.191 0±0.161 3)/(1.141 0±0.152 3)/(1.200 5±0.189 6) vs 1.809 7±0.253 4; 2 weeks TSLP-mRNA: (1.175 6±0.100 9)/(1.254 4±0.078 2)/(2.037 2±0.559 2) vs 4.582 9±0.697 7; 4 weeks TSLP-mRNA: (1.158 3±0.104 3)/(1.224 0±0.034 0)/(1.275 2±0.099 6) vs 4.814 4±0.662 8; all P<0.05), and not significantly different from control group. With the inhibition of TSLP, the concentrations of IL-4 and OVA-sIgE in rat serum were also decreased. Conclusion: 18ß-sodium glycyrrhetinic acid has obvious inhibitory effect on TSLP in nasal mucosa of AR rats, which can control Th2 type immune inflammatory reaction.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/biossíntese , Ácido Glicirretínico/farmacologia , Mucosa Nasal/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/imunologia , Animais , Citocinas/análise , Citocinas/imunologia , Feminino , Masculino , Mucosa Nasal/imunologia , Ratos , Ratos Wistar
4.
Clin Exp Rheumatol ; 37 Suppl 117(2): 122-129, 2019 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31162032

RESUMO

OBJECTIVES: To investigate whether expression of pro-inflammatory cytokines in the temporal artery may aid in differentiating biopsy-negative giant cell arteritis (GCA) patients from those with a negative biopsy without arteritis. METHODS: We investigated cytokine expression in temporal artery biopsy (TAB) of 54 consecutive patients: 17 with biopsy-positive GCA, 17 with biopsy-negative GCA, and 20 biopsy-negative without arteritis. We compared the expression rate of the following cytokines among these 3 groups of patients: interleukin-6 (IL-6), osteopontin (OPN), COX-2, and TNF-α. RESULTS: IL-6 was expressed in 13 (76%) patients with biopsy-positive GCA, 0 patients in biopsy-negative GCA, and 1(5%) patient with biopsy-negative without arteritis (p<0.05). OPN was expressed in 17 (100%) patients with biopsy-positive GCA, 2 (12%) patients with biopsy-negative GCA, and 0 patients with biopsy-negative without arteritis (p<0.05). Cox-2 was expressed in 16 (94%) patients with biopsy-positive GCA, 0 patients with biopsy-negative GCA, and 3 (15%) patients with biopsy-negative without arteritis (p<0.05). TNF- α was expressed in 17 (100%) patients with biopsy-positive GCA, 14 (82%) patients with biopsy-negative GCA, and 8 (40%) patients with biopsy-negative without arteritis (p<0.05). CONCLUSIONS: IL-6, COX-2 and OPN are significantly more expressed in the presence of a positive TAB compared to a negative TAB. TNF-α is significantly more expressed in GCA patients compared to non-GCA patients. Thus, TNF-α expression may suggest a diagnosis of GCA despite a negative TAB. Further larger studies are needed to confirm these findings.


Assuntos
Citocinas/metabolismo , Arterite de Células Gigantes , Artérias Temporais , Idoso , Biópsia , Citocinas/biossíntese , Feminino , Arterite de Células Gigantes/metabolismo , Arterite de Células Gigantes/patologia , Humanos , Masculino , Artérias Temporais/metabolismo , Artérias Temporais/patologia , Fator de Necrose Tumoral alfa
5.
Drug Des Devel Ther ; 13: 1163-1170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043769

RESUMO

Purpose: Umbelliferone (Umb), a member of coumarin family, is found in many plants and is a promising molecule with potential anti-inflammatory, anti-oxidative, and anti-tumor activities. However, the effect of Umb on arthritis remains unclear. Methods: A rat model with Freund's complete adjuvant (FCA)-induced arthritis was developed and used to test the efficacy of Umb on arthritis rats. Rats were given an intragastric injection of Umb (20 and 40 mg/kg) once daily from days 21 to 28 after the administration of FCA. Hind paw volume was assessed using a volume meter. The pro-inflammatory cytokine levels and prostaglandin E2 (PEG2) level in serum and synovial fluid were detected by ELISA. HE staining was used to determine representative histological changes in joint tissues, and Western blot analysis was employed to study the effects of Umb on MAPK/NF-κB signaling pathway. Results: Our results showed that Umb suppressed the release of IL-6, IL-1ß, tumor necrosis factor-alpha, and PEG2. In addition, Umb could also dramatically ameliorate the pathological changes observed in rat joints. Based on the results of Western blot, we also observed that Umb could strikingly suppress the expression of MAPK/NF-κB pathway molecules. Conclusion: These results proved that treatment with Umb is very effective for arthritis and inhibiting the MAPK/NF-κB signaling pathway may be a potential therapeutic target for treatment of arthritis.


Assuntos
Artrite Experimental/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Umbeliferonas/farmacologia , Animais , Artrite Experimental/metabolismo , Citocinas/biossíntese , Citocinas/sangue , Injeções Intraventriculares , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Umbeliferonas/administração & dosagem , Umbeliferonas/química
6.
Yonsei Med J ; 60(6): 500-508, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124332

RESUMO

PURPOSE: Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. MATERIALS AND METHODS: The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. RESULTS: miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. CONCLUSION: miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Apoptose , Glicina Hidroximetiltransferase/metabolismo , Células Matadoras Naturais/metabolismo , MicroRNAs/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Proliferação de Células , Citocinas/biossíntese , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética
7.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 37-42, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078150

RESUMO

Inflammation and insomnia are two types of symptoms very likely occur in life, seriously perplexing people's work and life. How to alleviate these symptoms is an urgent medical problem. Lucidone D (LUC) is a terpene from the ethanol extract of Ganoderma lucidum fruiting body. Triterpenoids are also the main pharmacological components of Ganoderma lucidum. In recent years, people pay more and more attention to its anti-inflammatory effect. In this study, LPS induced RAW264.7 macrophage inflammatory response model was used to evaluate the anti-inflammatory activity of LUC. The results showed that LUC could significantly inhibit the production of inflammatory mediators NO, which may play a role by down-regulating the expression level of iNOS and COX-2 proteins. Meanwhile, the production of TNF-α and IL-6 was significantly inhibited. These results indicate that LUC has obvious anti-inflammatory activity. Writhing and sedation tests in ICR male mice showed that LUC showed significant analgesic and sedative effects. In conclusion, these results suggest the anti-inflammatory, analgesic and sedative effects of LUC in vitro and in vivo.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Hipnóticos e Sedativos/farmacologia , Reishi/química , Terpenos/farmacologia , Analgésicos/química , Animais , Anti-Inflamatórios/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/biossíntese , Hipnóticos e Sedativos/química , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Pentobarbital , Células RAW 264.7 , Latência do Sono/efeitos dos fármacos , Terpenos/química
8.
Environ Pollut ; 250: 990-997, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31085486

RESUMO

In the present study, to assess the immunotoxicity of cypermethrin (CYP) in fish, Chinese rare minnows (Gobiocypris rarus) were exposed to environmentally relevant concentrations (0.15, 0.5, and 1.5 µg/L) of CYP for 28 d and subjected to pathogen challenge trials for 2 d. After 28 d of CYP exposure, the levels of Immunoglobulin M (IgM), Alkaline phosphatase (ALP), and C-reactive protein (CRP) were significantly decreased (p < 0.05) after treatment with 1.5 µg/L CYP. Moreover, an induction of inflammatory cytokine transcripts (tnfa, il-6, il-8, and il-12) was observed (p < 0.05) after treatment with 1.5 µg/L CYP. After challenge with Pseudomonas fluorescens (P. fluorescens), plasma lysozyme (LYS) activity at 24 and 48 hours post-injection (hpi) was significantly decreased in the 0.5 and 1.5 µg/L CYP treatment groups (p < 0.05). Moreover, liver Complement component 3 (C3) and CRP contents at 24 hpi were significantly decreased in the 1.5 µg/L CYP treatment group (p < 0.05), whereas significant decreases in liver C3 and IgM contents were observed at 48 hpi (p < 0.05). Inhibition of expression of Toll-like receptor-nuclear factor kappa B (TLR-NF-kB) signaling pathway-related genes was observed in the CYP treatment groups and resulted in significant down-regulation of inflammatory cytokines (il-1ß and il-12) in the 1.5 µg/L CYP treatment group at 48 hpi (p < 0.05). Interestingly, the mortality in the 0.5 and 1.5 µg/L CYP treatments was significantly increased at 48 hpi (p < 0.05). These results indicated that environmentally relevant concentrations of CYP suppressed the Chinese rare minnow immune system and reduced immune defense against bacterial infection, thereby causing subsequent mortality. Meanwhile, our results demonstrated that a subsequent host resistance challenge is an effective method for determining the immunotoxicity of chemicals (e.g., CYP).


Assuntos
Cyprinidae/imunologia , Doenças dos Peixes/microbiologia , Imunidade Inata/efeitos dos fármacos , Infecções por Pseudomonas/veterinária , Pseudomonas fluorescens/imunologia , Piretrinas/toxicidade , Fosfatase Alcalina/sangue , Animais , Proteína C-Reativa/metabolismo , Citocinas/biossíntese , Citocinas/genética , Imunoglobulina M/sangue , Fígado/metabolismo , Transdução de Sinais
9.
Medicine (Baltimore) ; 98(18): e15345, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045776

RESUMO

The brain has multiple functions, and its structures are very closely related to one another. Thus, the brain areas associated with stress, emotion, and intelligence are closely connected. The purpose of this study was to investigate the multiple associations between stress and emotional intelligence (EI), between EI and intelligence quotient (IQ), between cytokines and stress, and between cytokines and IQ. We measured the stress, EI, cognitive intelligence using IQ, and cytokine levels of 70 healthy subjects. We also analyzed the association of cytokines with IQ according to hemispheric dominance using the brain preference indicator (BPI). We found significant negative correlations between stress and the components of EI, such as emotional awareness and expression, emotional thinking, and emotional regulation. High levels of anger, which is a component of stress, were significantly related to poor emotional regulation. Additionally, emotional application was positively correlated with full-scale IQ scores and scores on the vocabulary, picture arrangement, and block design subtests of the IQ test. High IL-10 levels were significantly associated with low stress levels only in the right-brain-dominant group. High IL-10 and IFN-gamma levels have been associated with high scores of arithmetic intelligence. TNF-alpha and IL-6 were negatively associated with vocabulary scores and full-scale IQ, but IL-10 and IFN-gamma were positively associated with scores on the arithmetic subtest in left-brain-dominant subjects. On the other hand, IL-10 showed positive correlations with scores for vocabulary and for vocabulary and arithmetic in right-brain-dominant subjects. Furthermore, we found significant linear regression models which can show integrative associations and contribution on emotional and cognitive intelligence. Thus, we demonstrated that cytokines, stress, and emotional and cognitive intelligence are closely connected one another related to brain structure and functions. Also, the pro-inflammatory cytokines TNF-alpha and IL-6 had negative effects, whereas the anti-inflammatory cytokines (e.g., IL-10 and IFN-gamma) showed beneficial effects, on stress levels, and multiple dimensions of emotional and cognitive intelligence. Additionally, these relationships among cytokines, stress, and emotional and cognitive intelligence differed depending on right and left hemispheric dominance.


Assuntos
Cognição/fisiologia , Citocinas/biossíntese , Inteligência Emocional/fisiologia , Estresse Psicológico/fisiopatologia , Escalas de Wechsler , Adulto , Ira/fisiologia , Encéfalo/metabolismo , Dominância Cerebral/fisiologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Testes de Inteligência , Interferon gama/biossíntese , Interleucina-10 , Interleucina-6/biossíntese , Modelos Lineares , Masculino , República da Coreia , Fator de Necrose Tumoral alfa/biossíntese , Adulto Jovem
10.
Int J Mol Sci ; 20(7)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987036

RESUMO

Treatment with extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been suggested as novel therapeutic option in acute inflammation-associated disorders due to their immune-modulatory capacities. As we have previously observed differences in the cytokine profile of independent MSC-EV preparations, functional differences of MSC-EV preparations have to be considered. To evaluate the immune-modulatory capabilities of specific MSC-EV preparations, reliable assays are required to characterize the functionality of MSC-EV preparations prior to administration to a patient. To this end, we established an in vitro assay evaluating the immune-modulatory capacities of MSC-EV preparations. Here, we compared the efficacy of four independent MSC-EV preparations to modulate the induction of T cell differentiation and cytokine production after phorbol 12-myristate 13-acetate (PMA)/Ionomycin stimulation of peripheral blood mononuclear cells (PBMC) derived from six healthy donors. Flow cytometric analyses revealed that the four MSC-EV preparations differentially modulate the expression of surface markers, such as CD45RA, on CD4+ and CD8+ T cells, resulting in shifts in the frequencies of effector and effector memory T cells. Moreover, cytokine profile in T cell subsets was affected in a MSC-EV-specific manner exclusively in CD8+ naïve T cells. Strikingly, hierarchical clustering revealed that the T cell response towards the MSC-EV preparations largely varied among the different PBMC donors. Thus, besides defining functional activity of MSC-EV preparations, it will be crucial to test whether patients intended for treatment with MSC-EV preparations are in principal competent to respond to the envisioned MSC-EV therapy.


Assuntos
Vesículas Extracelulares/metabolismo , Imunomodulação , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular/efeitos dos fármacos , Análise por Conglomerados , Citocinas/biossíntese , Vesículas Extracelulares/efeitos dos fármacos , Humanos , Imunomodulação/efeitos dos fármacos , Ionomicina/farmacologia , Antígenos Comuns de Leucócito/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
11.
Biol Res ; 52(1): 22, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992075

RESUMO

BACKGROUND: Tumor microenvironment (TME) plays a vital role in determining the outcomes of radiotherapy. As an important component of TME, vascular endothelial cells are involved in the perivascular resistance niche (PVRN), which is formed by inflammation or cytokine production induced by ionizing radiation (IR). Protein kinase CK2 is a constitutively active serine/threonine kinase which plays a vital role in cell proliferation and inflammation. In this study, we investigated the potential role of CK2 in PVRN after IR exposure. RESULT: Specific CK2 inhibitors, Quinalizarin and CX-4945, were employed to effectively suppressed the kinase activity of CK2 in human umbilical vein endothelial cells (HUVECs) without affecting their viability. Results showing that conditioned medium from IR-exposed HUVECs increased cell viability of A549 and H460 cells, and the pretreatment of CK2 inhibitors slowed down such increment. The secretion of IL-8 and IL-6 in HUVECs was induced after exposure with IR, but significantly inhibited by the addition of CK2 inhibitors. Furthermore, IR exposure elevated the nuclear phosphorylated factor-κB (NF-κB) p65 expression in HUVECs, which was a master factor regulating cytokine production. But when pretreated with CK2 inhibitors, such elevation was significantly suppressed. CONCLUSION: This study indicated that protein kinase CK2 is involved in the key process of the IR induced perivascular resistant niche, namely cytokine production, by endothelial cells, which finally led to radioresistance of non-small cell lung cancer cells. Thus, the inhibition of CK2 may be a promising way to improve the outcomes of radiation in non-small cell lung cancer cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Caseína Quinase II/antagonistas & inibidores , Células Endoteliais/efeitos da radiação , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Antraquinonas/farmacologia , Western Blotting , Citocinas/biossíntese , Endotélio Vascular/citologia , Humanos , Naftiridinas/farmacologia
12.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987239

RESUMO

Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes and P. acnes-induced Toll-like receptor (TLR) 2-mediated inflammatory signaling in human keratinocytes. Secreted embryonic alkaline phosphatase assay confirmed that the anti-inflammatory activity of phloretin is associated with the P. acnes-stimulated TLR2-mediated NF-κB signaling pathway. Phloretin significantly decreased the level of phosphorylated c-Jun N-terminal kinase (JNK), showing a binding affinity of 1.184 × 10-5 M-1. We also found that phloretin binds with micromolar affinity to P. acnes ß-ketoacyl acyl carrier protein (ACP) synthase III (KAS III), an enzyme involved in fatty acid synthesis. Conformation-sensitive native polyacrylamide gel electrophoresis showed that phloretin reduced KAS III-mediated 3-ketoacyl ACP production by over 66%. A docking study revealed that phloretin interacts with the active sites of JNK1 and KAS III, suggesting their involvement in P. acnes-induced inflammation and their potential as targets for the antibacterial activity of phloretin. These results demonstrate that phloretin may be useful in the prevention or treatment of P. acnes infection.


Assuntos
Antibacterianos/farmacologia , Infecções por Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/microbiologia , Floretina/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Dermatopatias Bacterianas/metabolismo , Dermatopatias Bacterianas/microbiologia , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/antagonistas & inibidores , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antibacterianos/química , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Floretina/química , Propionibacterium acnes/enzimologia , Propionibacterium acnes/imunologia , Ligação Proteica , Dermatopatias Bacterianas/tratamento farmacológico , Relação Estrutura-Atividade , Receptor 2 Toll-Like/metabolismo
13.
Curr Protein Pept Sci ; 20(6): 505-524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30950347

RESUMO

α1-acid glycoprotein (orosomucoid, AGP) is an Acute Phase Protein produced by liver and peripheral tissues in response to systemic reaction to inflammation. AGP functions have been studied mostly in human, cattle and fish, although the protein has been also found in many mammalian species and birds. AGP fulfils at least two set of functions, which are apparently different from each other but in fact intimately linked. On one hand, AGP is an immunomodulatory protein. On the other hand, AGP is one of the most important binding proteins in plasma and, beside modulating pharmacokinetics and pharmacodynamics of many drugs, it is also able to bind and transport several endogen ligands related to inflammation. The focus of this review is the immunomodulatory activity of AGP. This protein regulates every single event related to inflammation, including binding of pathogens and modulating white blood cells activity throughout the entire leukocyte attacking sequence. The regulation of AGP activity is complex: the inflammation induces not only an increase in AGP serum concentration, but also a qualitative change in its carbohydrate moiety, generating a multitude of glycoforms, each of them with different, and sometimes opposite and contradictory, activities. We also present the most recent findings about the relationship between AGP and adipose tissue: AGP interacts with leptin receptor and, given its immunomodulatory function, it may be included among the potential players in the field of immunometabolism.


Assuntos
Fatores Imunológicos/imunologia , Orosomucoide/imunologia , Proteínas da Fase Aguda/metabolismo , Tecido Adiposo/imunologia , Animais , Quimiotaxia , Citocinas/biossíntese , Humanos , Fatores Imunológicos/metabolismo , Imunomodulação , Inflamação/imunologia , Inflamação/metabolismo , Orosomucoide/química , Orosomucoide/metabolismo , Conformação Proteica , Processamento de Proteína Pós-Traducional , Receptores para Leptina/metabolismo
14.
Biomed Res Int ; 2019: 9630793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941374

RESUMO

Background: A recombinant BCG strain expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (rBCG-S1PT), previously constructed by our research group, demonstrated the ability to develop high protection in mouse models of pertussis challenge which correlated with the induction of a Th1 immune response pattern. The Th1 immune response induced by rBCG-S1PT treatment was also confirmed in the murine orthotopic bladder cancer model, in which the intravesical instillation of rBCG-S1PT resulted in an improved antitumor effect. Based on these observations, we hypothesize that the reengineering of the S1PT expression in BCG could increase the efficiency of the protective Th1 immune response in order to develop a new alternative of immunotherapy in bladder cancer treatment. Objectives: To construct rBCG strains expressing S1PT from extrachromosomal (rBCG-S1PT) and integrative vectors (rBCG-Sli), or their combination, generating the bivalent strain (rBCG-S1+S1i), and to evaluate the respective immunogenicity of rBCG strains in mice. Methods: Mycobacterial plasmids were constructed by cloning the s1pt gene under integrative and extrachromosomal vectors and used to transform BCG, individually or in combination. Antigen expression and localization were confirmed by Western blot. Mice were immunized with wild-type BCG or the rBCG strains, and cytokines quantification and flow cytometry analysis were performed in splenocytes culture stimulated with mycobacterial-specific proteins. Findings: S1PT expression was confirmed in all rBCG strains. The extrachromosomal vector directs S1PT to the cell wall-associated fraction, while the integrative vector directs its expression mainly to the intracellular fraction. Higher levels of IFN-γ were observed in the splenocytes culture from the group immunized with rBCG-S1i in comparison to BCG or rBCG-S1PT. rBCG-S1+S1i showed higher levels of CD4+ IFN-γ + and double-positive CD4+ IFN-γ + TNF-α + T cells. Conclusions: rBCG-S1+S1i was able to express the two forms of S1PT and elicited higher induction of polyfunctional CD4+ T cells, indicating enhanced immunogenicity and suggesting its use as immunotherapy for bladder cancer.


Assuntos
Vacina BCG/imunologia , Linfócitos T CD4-Positivos/imunologia , Imunidade Celular , Mycobacterium bovis/fisiologia , Toxina Pertussis/metabolismo , Subunidades Proteicas/metabolismo , Vacinas Sintéticas/imunologia , Animais , Citocinas/biossíntese , Citocinas/metabolismo , Feminino , Imunização , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos BALB C , Fenótipo , Plasmídeos/metabolismo , Baço/citologia
15.
Biomed Res Int ; 2019: 3912142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949499

RESUMO

In the central nervous system and in the liver, the macrophage populations are represented exclusively by descendants of the hematopoietic progenitor cells of the yolk sac. The reasons for such differential distribution of macrophages are not fully understood. We found that, as can be judged by corresponding changes in the expression of CD86 and CD163 markers, the transient macrophages of monocytic lineage are more sensitive to activating stimuli. The two macrophage populations have distinct patterns of gene expression, which is particularly noticeable for M1- and M2-associated genes. For instance, Kupffer cells more readily develop and longer maintain the elevated expression levels of Il4, Il10, and Il13 upon the activation; by contrast, the macrophages of monocytic lineage express Il1b, Il12a, and Tnfα upon the activation. The obtained results allow us to conclude that the in vitro activated Kupffer cells of the liver are committed to M2 phenotype, whereas the in vitro activated monocyte-derived macrophages show a typical M1 behavior. These observations are likely to reflect the situation in the in vivo microenvironments.


Assuntos
Citocinas/biossíntese , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Macrófagos do Fígado/metabolismo , Ativação de Macrófagos , Monócitos/metabolismo , Animais , Macrófagos do Fígado/patologia , Masculino , Monócitos/patologia , Ratos , Ratos Wistar
16.
Biomed Res Int ; 2019: 3746326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30956980

RESUMO

Myricetin has been reported as a promising chemopreventive compound with multiple biofunctions. To evaluate its influence on gene expressions in genome-wide set and further investigate its anti-inflammatory property, the present study performed Gene Ontology and Ingenuity Pathway Analysis (IPA) to describe the basic gene expression characteristics by myricetin treatment in HepG2 cells, confirmed its multi-biofunction by real-time fluorescent quantitative PCR (RT-qPCR), and further verified its anti-inflammatory property by Western blotting and bio-plex-based cytokines assay. The IPA data showed that 337 gene expressions (48% of the top molecules) are disturbed over 2-fold, and the most possible biofunctions of myricetin are the effect on "cardiovascular disease, metabolic disease, and lipid metabolism," via regulation of 28 molecules with statistic score of 46. RT-qPCR data confirmed the accuracy of microarray data, and cytokines assay results indicated that 6 of the total 27 inflammatory cytokine secretions were significantly inhibited by myricetin pretreatment, including TNF-α, IFN-γ, IL-1α, IL-1ß, IL-2, and IL-6. The present study is the first time to elucidate the multi-function of myricetin in genome-wide set by IPA analysis and verify its anti-inflammatory property by proteomics of cytokines assay. Therefore, these results enrich the comprehensive bioactivities of myricetin and reveal that myricetin has powerful anti-inflammatory property, which provides encouragement for in vivo studies to verify its possible health benefits.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/biossíntese , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Western Blotting , Estudo de Associação Genômica Ampla , Células Hep G2 , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Proteômica
17.
Comp Immunol Microbiol Infect Dis ; 63: 136-141, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30961809

RESUMO

To investigate the correlation between avian tuberculosis and duck amyloidosis, the liver, lung, spleen, kidney, duodenum and pectoralis muscle of ducks naturally infected with Mycobacterium avium subsp. avium were used to detect amyloidosis by Congo red staining and potassium permanganate-Congo red staining. The expression level of IL-1ß, IL-6, IL-10, TNF-α and SAA2 were detected by quantitative real-time RT-PCR (qRT-PCR). The results showed that the liver, lung, spleen, kidney, duodenum and pectoralis muscle of the infected ducks exhibited amyloid proteins under ordinary light microscopy and the polarization light under polarized light microscopy. However, no amyloid deposition in potassium permanganate-Congo red staining sections indicated that the amyloidosis was AA amyloidosis. In addition, the expression level of IL-1ß, IL-6, IL-10, TNF-α and SAA2 increased from 4 to 43. This study showed that avian tuberculosis could induce secondary amyloidosis in naturally infected ducks.


Assuntos
Amiloidose/epidemiologia , Amiloidose/veterinária , Mycobacterium avium/patogenicidade , Placa Amiloide/patologia , Proteína Amiloide A Sérica/metabolismo , Tuberculose Aviária/patologia , Amiloidose/patologia , Animais , Citocinas/biossíntese , Patos , Duodeno/metabolismo , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Músculos Peitorais/metabolismo , Placa Amiloide/veterinária , Baço/metabolismo , Tuberculose Aviária/microbiologia
18.
Scand J Immunol ; 89(6): e12761, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977163

RESUMO

Interleukin-21 (IL-21) is a type I cytokine produced by activated T cells that promotes cytokine production in monocytes. Monocytes are activated by Toll-like receptors (TLRs) to produce pro-inflammatory mediators. However, little is known about the regulatory effect of IL-21 on TLR-mediated inflammation in human monocytes. This study investigated the potential association between IL-21 and TLR2/4-mediated inflammation in human monocytic THP-1 cells. First, the expression of the IL-21 receptor (IL-21R) in human monocytic THP-1 cells was examined by flow cytometry. Then, THP-1 cells were treated with either the TLR2 ligand peptidoglycan (PGN) or the TLR4 ligand lipopolysaccharide (LPS) with or without IL-21. Then, the production of several cytokines (IL-6, IL-8, TNF-α, IFN-γ and IL-10), expression of TLR2/4, and activation of the downstream signaling pathways of mitogen-activated protein kinase (MAPK), Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor-kappa B (NF-κB) were determined. We found that IL-21R was highly expressed in human monocytic THP-1 cells and that IL-21 induced TLR2 and TLR4 expression and further enhanced PGN/LPS-mediated TLR2/4 expression. In addition, IL-21 also upregulated the expression of IL-6, IL-8, TNF-α, IFN-γ and IL-10 and enhanced TLR2/4-mediated cytokine production in THP-1 cells via phosphorylation of the STAT3, Akt and p38 MAPK signalling pathways. Our study suggests, for the first time that IL-21 enhances TLR2/4-mediated cytokine production in human monocytic THP-1 cells by activating the STAT3, PI3K/Akt and p38 MAPK signalling pathways.


Assuntos
Citocinas/biossíntese , Interleucinas/imunologia , Monócitos/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Linhagem Celular Tumoral , Humanos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Interleucina-21/biossíntese , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células THP-1 , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Int Arch Allergy Immunol ; 179(1): 43-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943513

RESUMO

BACKGROUND: The aim of this study was to investigate the role of Notch-1 signaling through Notch-1 ligands on bronchial epithelial cells (BECs) in regulating the development of T helper 2 (Th2) lymphocytes after RSV infection. METHODS: Firstly, we analyzed the expression of cytokines and Notch-1 ligands in BECs by using real-time PCR. Then, RSV-infected BECs were co-cultured with CD4+ T cells in a transwell chamber for 48 h, and differentiation of T cells in the lower chamber was determined using flow cytometry and real-time PCR. JAG1 siRNA was then used to determine the effects of Jagged/Notch-1 signaling on the differentiation of Th2. An RSV-infected mouse model was also used to analyze the secretion of Th differentiation-associated cytokines in serum and lung tissues using ELISA, the histopathological changes using HE staining, and the expression of JAG1 and JAG2 in BECs. RESULTS: The results showed that RSV promoted the expression of Th2-type cytokines and Jagged-1 and inhibited the expression of Jagged-2 in normal BECs. RSV-infected BECs induced Th2 differentiation. In addition, JAG1 downregulation inhibited the differentiation of Th2 and promoted differentiation of Th1. In the RSV-infected mouse model, the RSV titer, inflammation decreased with time. IL-4 and IL-17 increased on day 28 and 60, while IFNγ increased on day 7 and 28. Moreover, the expression of Jagged-1 increased and that of Jagged-2 decreased in BECs, which was consistent with IL-4 production in lung tissues. CONCLUSION: Our data showed that BECs had the potential to promote the differentiation of Th2 lymphocytes through Jagged-1/Notch-1 signaling.


Assuntos
Brônquios/fisiologia , Proteína Jagged-1/fisiologia , Proteína Jagged-2/fisiologia , Receptor Notch1/fisiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Transdução de Sinais/fisiologia , Células Th2/citologia , Animais , Brônquios/imunologia , Brônquios/patologia , Diferenciação Celular , Citocinas/biossíntese , Células Epiteliais/fisiologia , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Parasitol Res ; 118(5): 1343-1352, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30941496

RESUMO

The peritoneal cavity has a microenvironment capable of promoting proliferation, differentiation, and activation of the resident cells and recruitment of blood cells through the capillary network involved in the peritoneum. Among the cells found in the peritoneal cavity, B-1 cells are a particular cell type that contains features that are not very well defined. These cells differ from conventional B lymphocytes (B-2) by phenotypic, functional, and molecular characteristics. B-1 cells can produce natural antibodies, migrate to the inflammatory focus, and have the ability to phagocytose pathogens. However, the role of B-1 cells in immunity against parasites is still not completely understood. Several experimental models have demonstrated that B-1 cells can affect the susceptibility or resistance to parasite infections depending on the model and species. Here, we review the literature to provide information on the peculiarities of B-1 lymphocytes as well as their interaction with parasites.


Assuntos
Subpopulações de Linfócitos B/imunologia , Helmintíase/imunologia , Helmintos/imunologia , Imunidade Humoral/imunologia , Parasitos/imunologia , Cavidade Peritoneal/citologia , Infecções por Protozoários/imunologia , Animais , Citocinas/biossíntese , Citocinas/imunologia , Helmintíase/parasitologia , Humanos , Camundongos , Peritônio/citologia , Peritônio/imunologia , Infecções por Protozoários/parasitologia
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