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1.
Anticancer Res ; 39(8): 4503-4509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366552

RESUMO

BACKGROUND/AIM: Oral administration of Pantoea agglomerans-derived lipopolysaccharide (LPSp) has been reported to have a preventive effect against various lifestyle-related diseases. Therefore, we examined the preventive effect on high blood pressure, which is a kind of reserve arm for lifestyle-related diseases. MATERIALS AND METHODS: Spontaneous hypertensive rat (SHR) and WKY rat were bred from 6 to 16 weeks of age. SHR were orally administered 100 µg/kg LPSp and 0.1% NaCl, and blood pressure was measured at 6, 10, 13 and 16 weeks. Furthermore, at 16 weeks of age, blood biochemical markers were measured and microbial community composition was analyzed. RESULTS: SHRs developed hypertension with age, which was exacerbated by salt loading. Although there was almost no reduction in blood pressure in SHRs that received LPSp. It was suppressed at 13-16 weeks of age in those with salt loading. CONCLUSION: Oral administration of LPSp showed a preventive effect on salt-loaded hypertension.


Assuntos
Citocinas/genética , Hipertensão/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hipertensão/genética , Hipertensão/patologia , Lipopolissacarídeos/química , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Sais/toxicidade
2.
Life Sci ; 234: 116778, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430454

RESUMO

AIMS: To clarify the role of the gut-brain axis in depression. MAIN METHODS: We used the iTRAQ technique to identify differential proteins in the intestine of the rat model of chronic unpredictable mild stress (CUMS)-induced depression. Significant differential proteins were subjected to Gene Ontology (GO) functional annotations and KEGG pathway enrichment analysis. Key proteins were validated at the mRNA and protein levels. The levels of cytokines in the intestine, serum and hypothalamus were examined by ELISA. HPLC-UV was used to detect the levels of amino acids. KEY FINDINGS: In the rat intestine, 349 differential proteins (209 downregulated, 140 upregulated) were identified. GO analysis indicated that "protein complex assembly" was the first-ranked biological process. SNARE complex components, including SNAP23, VAMP3 and VAMP8, were increased at the mRNA levels, while only VAMP3 and VAMP8 were also upregulated at the protein level. TNFα, IL6 and IL1ß were upregulated in the CUMS rat intestine, while TNFα was decreased in the serum and hypothalamus. IL1ß was decreased in the serum. "Protein digestion and absorption" was the most significantly enriched KEGG pathway, involving 5 differential proteins: SLC9A3, ANPEP, LAT1, ASCT2 and B0AT1. Glutamine, glycine and aspartic acid were perturbed in the CUMS rat intestine. SIGNIFICANCE: Our findings suggest that CUMS enhances the adaptive immune response in the intestine through ER-phagosome pathway mediated by SNARE complex and disturb absorption of amino acids. It advances our understanding of the role of gut-brain axis in depression and provides a potential therapeutic target for the disease.


Assuntos
Aminoácidos/análise , Citocinas/análise , Depressão/patologia , Mucosa Intestinal/metabolismo , Intestinos/patologia , Proteínas SNARE/análise , Aminoácidos/metabolismo , Animais , Citocinas/genética , Depressão/etiologia , Depressão/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Absorção Intestinal , Masculino , Proteômica , Ratos , Ratos Sprague-Dawley , Proteínas SNARE/genética , Estresse Psicológico/complicações
3.
Zhonghua Yi Xue Za Zhi ; 99(25): 1963-1967, 2019 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-31269601

RESUMO

Objective: To investigate the cinical value of FAM19A4promoter methylation in cervicalexfoliated cells for triage of cervical cancer. Methods: A total of 162 high-risk HPV-infected patients who were pathologically confirmed as different cervical lesions from August 2017 to December 2017 were collected in Guangdong Women and Children Hospital. Taqman probe-based quantitative PCR (qPCR) was used to detect the methylation of FAM19A4 promoterin different grades of cervical lesions, and the value of FAM19A4 methylation in predicting cervical HSIL and the above lesions was calculated by diagnostic test. Results: (1)The positive rates of FAM19A4 methylation in cervical exfoliated cells increased with the severity of cervical lesions, which were 7.69% (4/52) , 34.62% (9/26) , 55.56% (20/36) , 95.83% (46/48) in normal cervix/cervicitis, cervical LSIL, HSIL, and cervical cancer, respectively(P<0.05).(2)There was no significant difference in the detection rates of FAM19A4 methylation between different age groups, pathological types, clinical stage, tumor size and lymph node metastasis status (P>0.05). (3) The specificity and positive predictive value of FAM19A4 methylation in detecting cervical HSIL alone and ≥HSIL lesions were the optimal, with the AUC of 0.69 and 0.84, respectively. When combined with HPV16/18 genotyping, the sensitivity was significantly improved. Conclusions: The detection of FAM19A4 promoter methylation in cervical exfoliated cells has a high clinical value of discriminating ≥HSIL lesions; and the cotest of methylated FAM19A4 and HPV16/18 genotyping can identify ≥HSIL lesions more sensitively.


Assuntos
Neoplasia Intraepitelial Cervical , Citocinas/genética , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Metilação de DNA , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Regiões Promotoras Genéticas
4.
Nat Commun ; 10(1): 2924, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266950

RESUMO

Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-ß activation. In addition, PKC-ß also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.


Assuntos
Diferenciação Celular , Doenças Inflamatórias Intestinais/imunologia , Transdução de Sinais , Linfócitos T Reguladores/citologia , Receptor fas/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , NF-kappa B/genética , NF-kappa B/imunologia , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/imunologia , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Proteína Quinase C beta/genética , Proteína Quinase C beta/imunologia , Linfócitos T Reguladores/imunologia , Receptor fas/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
5.
Zool Res ; 40(4): 317-323, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31310065

RESUMO

Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditions. However, its role in atherosclerosis remains undefined. In this study, we administered vehicle or LECT2 to male Apoe-/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8, IL-1ß, and TNF-α were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-α, IL-1ß, IL-8, MCP-1, and MMP-1 concentrations were measured by enzyme-linked immunosorbent assay. CD68, CD31, and α-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immunostaining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-α, IL-8, and IL-1ß mRNA abundance. Furthermore, LECT2 decreased CD68, but increased α-SMA in atherosclerotic lesions, suggesting an increase in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.


Assuntos
Aterosclerose/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória
6.
BMC Vet Res ; 15(1): 234, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286936

RESUMO

BACKGROUND: Enterotoxigenic Escherichia coli K88 (E. coli K88) are considered as a major cause of diarrhea and death in newly weaned piglets. Oral passive immunization with chicken egg yolk immunoglobulins (IgY) have attracted considerable attention for treatment of gastrointestinal infection due to its high specificity. In this study it was estimated the protective effect of anti-K88 fimbriae IgY against E. coli K88 adhesion to piglet intestinal mucus in vitro and to investigate the potential use of IgY for controlling E. coli-induced diarrhea in weaned piglets in vivo. RESULTS: E. coli K88 was incubated with IgY for 24 h, and the bacterial growth profiles showed that specific IgY with a concentration higher than 5 mg/mL was observed to significantly inhibit the growth of E. coli K88 compared to nonspecific yolk powder in a liquid medium. Moreover, pretreatment with 50 mg/mL of IgY was found to significantly decrease the adhesion ability of E. coli K88 to porcine jejunal and ileal mucus, further supported by the observations from our immunofluorescence microscopic analysis. In vivo, administration of IgY successfully protected piglets from diarrhea caused by E. coli K88 challenge. Additionally, IgY treatment efficiently alleviated E. coli-induced intestinal inflammation in piglets as the gene expression levels of inflammatory cytokines TNF-α, IL-22, IL-6 and IL-1ß in IgY-treated piglets remained unchanged after E. coli K88 infection. Furthermore, IgY significantly prevented E. coli K88 adhering to the jejunal and ileal mucosa of piglets with E. coli infection and significantly decreased E. coli and enterotoxin expression in colonic contents. CONCLUSION: Outcome of the study demonstrated that IgY against the fimbrial antigen K88 was able to significantly inhibit the growth of E. coli K88, block the binding of E. coli to small intestinal mucus, and protect piglets from E. coli-induced diarrhea. These results indicate that passive immunization with IgY may be useful to prevent bacterial colonization and to control enteric diseases due to E. coli infection. The study has great clinical implication to provide alternative therapy to antibiotics in E coli induced diarrhea.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Diarreia/etiologia , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/complicações , Imunoglobulinas/farmacologia , Animais , Antígenos de Bactérias/imunologia , Citocinas/genética , Diarreia/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/imunologia , Proteínas de Fímbrias/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Imunização Passiva , Imunoglobulinas/uso terapêutico , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Ligação Proteica/efeitos dos fármacos , Suínos
7.
Life Sci ; 233: 116685, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31348947

RESUMO

AIMS: The present study aimed to investigate the effects of laser irradiation on the growth factors and cell apoptosis of in vitro cultured infant hemangioma endothelial cells. MAIN METHODS: Endothelial cells of infant hemangioma were cultured in vitro and irradiated using a variable pulse width 1064 nm Nd:YAG laser and intense pulsed light (IPL), the expression of VEGF, VEGFR-2, bFGF and their mRNAs before and after irradiation were measured by ELISA, western blot, RT-PCR and flow cytometry, and changes in the apoptotic rate of endothelial cells in hemangioma were monitored. KEY FINDINGS: The mRNA and protein expressions of VEGF, VEGFR-2, bFGF in hemangioma endothelial cells were inhibited by both Nd:YAG laser and ILP compared to the control cells. The apoptotic rates of hemangioma endothelial cells were also decreased after both laser irradiation treatments in comparison to the blank group. The differences were statistically significant. SIGNIFICANCE: Laser irradiation treats hemangioma not only through a selective photothermal mechanism, but also through cytokine signaling pathways.


Assuntos
Apoptose/efeitos da radiação , Células Endoteliais/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Hemangioma/metabolismo , Hemangioma/patologia , Terapia a Laser/métodos , Proliferação de Células , Citocinas/genética , Citocinas/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Hemangioma/radioterapia , Humanos , Técnicas In Vitro , Lactente , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
8.
J Sci Food Agric ; 99(13): 5870-5880, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206687

RESUMO

BACKGROUND: Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such as ß-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti-inflammatory activity of the association of these two compounds. RESULTS: Treatment with BCP-DHA, at a dose of 200 µL/animal, significantly inhibited the migration of neutrophils in a Cg-induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP-DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF-α and IFN-γ in treated groups, an increase of IL-4 and IL-5 in B/D and B/D + SA groups, and an augmentation of IL-6 and IL-12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups. CONCLUSION: In general, the BCP-DHA association presented anti-inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Peritonite/tratamento farmacológico , Sepse/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Peritonite/genética , Peritonite/imunologia , Peritonite/microbiologia , Sepse/genética , Sepse/imunologia , Sepse/microbiologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
9.
Nat Commun ; 10(1): 2882, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253783

RESUMO

NLR Family CARD Domain Containing 5 (NLRC5), an important immune regulator in innate immunity, is involved in regulating inflammation and antigen presentation. However, the role of NLRC5 in vascular remodeling remains unknown. Here we report the role of NLRC5 on vascular remodeling and provide a better understanding of its underlying mechanism. Nlrc5 knockout (Nlrc5-/-) mice exhibit more severe intimal hyperplasia compared with wild-type mice after carotid ligation. Ex vivo data shows that NLRC5 deficiency leads to increased proliferation and migration of human aortic smooth muscle cells (HASMCs). NLRC5 binds to PPARγ and inhibits HASMC dedifferentiation. NACHT domain of NLRC5 is essential for the interaction with PPARγ and stimulation of PPARγ activity. Pioglitazone significantly rescues excessive intimal hyperplasia in Nlrc5-/- mice and attenuates the increased proliferation and dedifferentiation in NLRC5-deficient HASMCs. Our study demonstrates that NLRC5 regulates vascular remodeling by directly inhibiting SMC dysfunction via its interaction with PPARγ.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Túnica Íntima/metabolismo , Animais , Aorta , Apoptose , Pressão Sanguínea , Transplante de Medula Óssea , Proliferação de Células , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Frequência Cardíaca , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Miócitos de Músculo Liso/metabolismo , Plasmídeos , Transcriptoma , Remodelação Vascular
10.
Chem Biol Interact ; 309: 108718, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31211952

RESUMO

We have previously reported the isolation of four compounds, caffeoyloxy-5,6-dihydro-4-methyl-(2H)-pyran-2-one (CDMP), olinioside, caffeic acid and 3-hydroxylup-12-en-28-oic acid, from the leaves of Olinia usambarensis. Here, we evaluated the inhibitory effects of these compounds on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 macrophages, and found that CDMP is the most potent of these two pro-inflammatory mediators (IC50; 12.12 µM and 10.78 µM, respectively). Consistent with these results, CDMP also down-regulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6) at the protein and mRNA levels in LPS-treated RAW 264.7 macrophages. Furthermore, CDMP suppressed LPS-induced nuclear factor κB (NF-κB) activation by decreasing p65 nuclear translocation through the phosphorylation and degradation of the inhibitory κBα (IκBα). CDMP also attenuated LPS-induced transcriptional and DNA-binding activities of activator protein 1 (AP-1) by suppressing the phosphorylation and expression of c-Fos and c-Jun. Finally, CDMP considerably suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), but did not affect the phosphorylation of p38 or extracellular signal-regulated kinase (ERK). Taken together, our data suggest that CDMP down-regulates genes encoding pro-inflammatory mediators and cytokines, such as iNOS, COX-2, TNF-α, IL-1ß, and IL-6 via NF-κB and JNK/AP-1 inactivation in LPS-induced RAW 264.7 macrophages.


Assuntos
Mediadores da Inflamação/metabolismo , Myrtales/química , NF-kappa B/metabolismo , Piranos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Myrtales/metabolismo , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Piranos/química , Células RAW 264.7 , Fator de Transcrição AP-1/antagonistas & inibidores
11.
Virol J ; 16(1): 79, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196204

RESUMO

BACKGROUND: The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population. METHODS: Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1ß, IL-17, IL-10 and IL-28 genes. RESULTS: The frequencies of the IL-1ß rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008). CONCLUSIONS: This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.


Assuntos
Citocinas/genética , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Citocinas/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza B , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
J Microbiol Biotechnol ; 29(7): 1022-1032, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31216608

RESUMO

Probiotics are known to provide the host with immune-modulatory effects and are therefore of remarkable interest for therapeutic and prophylactic applications against various disorders, including inflammatory diseases. Weissella cibaria JW15 (JW15) has been reported to possess probiotic and antioxidant properties. However, the effect of JW15 on inflammatory responses has not yet been reported. Therefore, the objective of the current study was to evaluate the anti-inflammatory potential of JW15 against lipopolysaccharide (LPS) stimulation. The production of pro-inflammatory factors and the cellular signaling pathways following treatment with heat-killed JW15 was examined in LPS-induced RAW 264.7 cells. Treatment with heat-killed JW15 decreased nitric oxide and prostaglandin E2 production via downregulation of the inducible nitric oxide synthase and cyclooxygenase-2. In addition, treatment with heat-killed JW15 suppressed the expression of pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. The anti-inflammatory properties of treating with heat-killed JW15 were associated with mitogen-activated protein kinase signaling pathwaymediated suppression of nuclear factor-κB. These results indicated that JW15 possesses antiinflammatory potential and provide a molecular basis regarding the development of functional probiotic products.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Probióticos/farmacologia , Fator de Transcrição RelA/metabolismo , Weissella/fisiologia , Animais , Sobrevivência Celular , Ciclo-Oxigenase 2/genética , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Alimentos Fermentados/microbiologia , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
13.
J Agric Food Chem ; 67(26): 7485-7495, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31180669

RESUMO

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, contaminating in a wide variety of foods and feeds. Mycotoxins, including OTA, could cause immunosuppression in almost all previous studies in vivo. However, the vast majority of results in vitro showed that mycotoxins caused immunostimulation. Why the results of studies in vitro are contrary to studies in vivo is unknown. Our study aims to explore the underlying reason and mechanism of the paradoxical effect. In this study, porcine alveolar macrophage cell line 3D4/21 was chosen as an in vitro model and treated with 1.0 µg/mL OTA for different times. Some indexes, such as expression of inflammatory cytokines, migration, phagocytosis, macrophage polarization, autophagy-related proteins, and Akt1 phosphorylation, were detected. The results showed that pro-inflammatory cytokine expression, migration, and phagocytosis were increased, with macrophage polarization to the M1 phenotype at 24 h of OTA exposure. Surprisedly, anti-inflammatory cytokine expression was increased, cell phagocytosis and migration were decreased, and macrophage polarization was switched from M1 to M2 at 72 h of OTA exposure. Furthermore, we found that long-time exposure of OTA also suppressed autophagy, and the autophagy activator blocked the OTA-induced immunosuppression. Phosphorylation of Akt1 plays a positive role in autophagy inhibition. In conclusion, long-time instead of short-time exposure of OTA in vitro induced immunosuppression. The immunosuppression mechanism of OTA in vitro involved inhibition of autophagy through upregulating p-Akt1. Our results provide new insight into research on the mechanism of mycotoxin-induced immunosuppression in vitro.


Assuntos
Imunossupressores/toxicidade , Macrófagos Alveolares/efeitos dos fármacos , Ocratoxinas/toxicidade , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/imunologia , Imunossupressores/administração & dosagem , Macrófagos Alveolares/imunologia , Ocratoxinas/administração & dosagem , Fagocitose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Suínos , Fatores de Tempo
14.
Vet Microbiol ; 233: 124-132, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176398

RESUMO

Leptospirosis is a zoonosis, caused by pathogenic spirochetes of the genus Leptospira. Although cattle are usually the maintenance hosts of serovar Hardjo, Pomona is the most frequent serovar circulating in Argentina. The understanding of bovine innate immune response and the virulence of this serovar is important for future control measures. This work compares infection of bovine macrophages with the virulent L. interrogans sv Pomona strain AKRFB (P1) and its attenuated counterpart (P19). First, we confirmed attenuation in the hamster model. Mortality and lung hemorrhages occurred after P1 inoculation, while the survival rate was 100% in P19-infected animals. Cells infected with both strains showed statistically upregulated gene expression of pro-inflammatory cytokines, IL-1ß, IL-6 and TNFα. The level of expression of anti-inflammatory cytokine IL-10 was statistically different between strains. Increased expression of IL-10 was observed only in P1-infected cells. For the first time, we describe macrophages extracellular traps induced by infection of bovine macrophages (bMETs) with both, the virulent and attenuated Leptospira interrogans Pomona strains. P1 was found higher internalized when the phagocytosis was inhibited, suggesting a cell entrance of this strain also by an independent-phagocytosis pathway. Furthermore, P1 was higher colocalized with acidic and late endosomal compartments compared with P19. This data emphasizes the importance to deepen in Leptospira bovine macrophages particular invasion mechanisms and, furthermore, underline the value of studying the main hosts.


Assuntos
Imunidade Inata , Leptospira interrogans serovar pomona/patogenicidade , Macrófagos/imunologia , Macrófagos/microbiologia , Animais , Argentina , Bovinos , Células Cultivadas , Cricetinae , Citocinas/genética , Citocinas/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Leptospirose/imunologia , Pulmão/microbiologia , Pulmão/patologia , Sorogrupo , Virulência
15.
Vet Microbiol ; 233: 93-101, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176418

RESUMO

Actinobacillus pleuropneumoniae (APP) and porcine circovirus type 2 (PCV2) are both important pathogens of the porcine respiratory disease complex (PRDC), which results in significant worldwide economic losses. Recently, PCV2 and APP coinfection has been described in the worldwide pork industry, and represents an extremely complex situation in veterinary medicine. However, the mechanism of their coinfection has not been investigated. In this study, we found that PCV2 promoted APP adhesion to and invasion of porcine alveolar macrophages (PAMs) during coinfection. Additionally, PCV2 suppressed reactive oxygen species (ROS) production by inhibiting cytomembrane NADPH oxidase activity, which was beneficial for APP survival in PAMs in vitro. During coinfection, PCV2 weakened the inflammatory response and macrophage antigen presentation by decreasing TNF-α, IFN-γ and IL-4 expression, and reduced clearance of the invading bacteria. The host-cell experimental results were verified in a mouse model. The findings provide a deeper and novel understanding of porcine coinfection, and will be extremely helpful for the design of strategies for PRDC control.


Assuntos
Actinobacillus pleuropneumoniae/fisiologia , Circovirus/fisiologia , Coinfecção/veterinária , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/virologia , Espécies Reativas de Oxigênio/metabolismo , Infecções por Actinobacillus/imunologia , Infecções por Actinobacillus/veterinária , Animais , Anticorpos Antivirais/imunologia , Apresentação do Antígeno , Aderência Bacteriana , Infecções por Circoviridae/imunologia , Infecções por Circoviridae/veterinária , Citocinas/genética , Citocinas/imunologia , Feminino , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos ICR , Viabilidade Microbiana , NADPH Oxidases/metabolismo , Suínos
16.
Acta Virol ; 63(2): 186-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230447

RESUMO

Little is known about the role of genetic variation in the genes for cytokines and susceptibility to viral infection especially torque teno virus (TTV) following allogeneic hematopoietic stem cell transplantation. In this study, the association between interleukin-12, interleukin-17, interleukin-10 (IL-12,-17,-10) and tumor necrosis factor-α (TNF-α) polymorphisms was evaluated in patients with TTV infection who underwent allogeneic hematopoietic stem cell transplantation from South of Iran. The single nucleotide polymorphisms in the cytokine genes including IL-12 (-1188A/C), IL-17 (-197G/A), IL-10 (-1082G/A, -819C/T and -592C/A) and TNF-α (-308 G/A) were analyzed by PCR-RFLP methods. While our results did not show any association between IL-17, IL-12 and IL-10 (-819C/T and -1082G/A) polymorphisms and TTV infection status, heterozygote genotype of IL-10 (-592C/A) had direct correlation with TTV infection and A allele of TNF-α (-308G/A) showed a protective effect against TTV infection (P = 0.05 and P = 0.025, respectively). Within the group of patients who experienced acute graft-versus-host disease, the AA genotype and the A allele of IL-17 (-197 G/A) were significantly higher in non-infected patients compared to infected ones (P = 0.024 and P = 0.057, respectively). It was also observed that among infected patients, the GG genotype of IL-17 and AA genotype of TNF-α were significantly increased in hematopoietic stem cell transplanted patients with low grade (grade I+II) acute graft-versus-host disease compared to high grade (grade III and IV) disease (P = 0.056 and P = 0.056, respectively). Taken together, genetic variation of IL-10 (-592C/A) and TNF-α (-308G/A) genes might be associated with susceptibility to TTV infection post hematopoietic stem cell transplantation. Keywords: TNF-α; interleukins; torque teno virus (TTV); hematopoietic stem cell transplantation (HSCT); graft versus host disease (GvHD).


Assuntos
Citocinas , Infecções por Vírus de DNA , Transplante de Células-Tronco Hematopoéticas , Torque teno virus , Citocinas/genética , Infecções por Vírus de DNA/genética , Humanos , Interleucina-10/genética , Interleucina-12/genética , Interleucina-17/genética , Irã (Geográfico) , Fator de Necrose Tumoral alfa/genética
17.
Gene ; 710: 114-121, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31153885

RESUMO

Mastitis impairs animal health and results in economic loss. Lipopolysaccharide (LPS) may cause immune response and inflammation in the bovine mammary gland. Hydrogen sulfide (H2S) is the third gasotransmitter that acts as an anti-inflammation regulator in many cells. Despite the importance of H2S in regulating inflammation, the effect and mechanism of exogenous H2S on LPS-induced inflammation in bovine mammary epithelial cells are unknown. In the present study, with NaHS as a donor of H2S, the bovine mammary epithelial cell line (MAC-T) was applied as an in vitro model to study the role of H2S on LPS-induced MAC-T cells. The results verified that the cell viability was diminished by LPS but restored by exogenous H2S at a physiologically relevant concentration (10 µM). Additionally, the production of H2S was mitigated in the LPS-induced MAC-T cells. Meanwhile, exogenous H2S decreased the intracellular ROS production and mRNA expression levels of the pro-inflammatory cytokines, TNF-α, IL-1ß, IL-8, and IL-6. Furthermore, exogenous H2S inhibited the mRNA expression of TLR4 and activation of NF-κB signaling pathway. In summary, exogenous H2S exerts anti-inflammatory effects through attenuating oxidative stress and blocking the TLR4/NF-κB pathway in the LPS-induced bovine mammary epithelial cells. Our findings might clarify new prophylactic approaches for mastitis.


Assuntos
Anti-Inflamatórios/farmacologia , Sulfeto de Hidrogênio/farmacologia , Lipopolissacarídeos/efeitos adversos , Glândulas Mamárias Animais/citologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular , Citocinas/genética , Regulação para Baixo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/imunologia , NF-kappa B/genética , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
18.
Food Chem ; 293: 491-498, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151640

RESUMO

Synthetic food preservatives like sodium acetate (SA), sodium benzoate (SB), potassium sorbate (PS) and Butyl paraben (BP) have been widely used in food and pharmacy industries. One of the toxicological aspects of food additives is evaluation of their interaction with serum proteins such as albumin. These additives interaction with human serum albumin (HSA) can exert considerable effect on the absorption, distribution, metabolism and toxicity of chemical compounds. It should be noticed that the aforementioned food preservatives intake increase mainly in the presence of glucose may lead to complex formation of SA, SB, PS and BP with HSA and accelerate the development of variety disease such as cancer, diabetes, multiple sclerosis, brain damage, nausea and cardiac disease. Therefore, to understand the mechanisms of aforementioned food additives interaction and conformational changes of proteins, we aim to review various studies that investigated albumin interaction with these additives using several procedures.


Assuntos
Conservantes de Alimentos/química , Albumina Sérica/química , Citocinas/genética , Citocinas/metabolismo , Dano ao DNA/efeitos dos fármacos , Conservantes de Alimentos/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Parabenos/química , Parabenos/toxicidade , Acetato de Sódio/química , Acetato de Sódio/toxicidade , Benzoato de Sódio/química , Benzoato de Sódio/toxicidade , Ácido Sórbico/química , Ácido Sórbico/toxicidade
19.
Anticancer Res ; 39(5): 2385-2394, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092431

RESUMO

BACKGROUND: Most patients with head and neck cancer receive nonsteroidal anti-inflammatory drugs concomitant with oncogenic treatment in order to control cardiovascular diseases and chronic inflammatory processes. Inflammation is closely related to neoplastic development and the release of inflammatory cytokines and chemokines represents a crucial event in this relationship. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) and celecoxib treatment in the gene expression pattern of cytokines and chemokines in squamous cell carcinoma (OSCC) cell lines. MATERIALS AND METHODS: Cells were treated with plasmatic concentrations of ASA and celecoxib and were submitted to cell viability assay and immunoenzymatic assay to investigate interleukin 6 (IL6) production. Treated cells were collected and a gene expression array was performed using the reverse transcriptase-quantitative polymerase chain reaction. RESULTS: Both treatments provoked a discrete inhibitory effect on cell viability and modulated IL6 production. The mRNA expression of several cytokines, chemokines, chemokine receptors, and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib. CONCLUSION: Plasmatic doses of ASA and celecoxib altered the expression of IL6 and the gene expression of chemokines (ligands and receptors) and cytokines in a dose- and time-dependent manner.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Interleucina-6/genética , Neoplasias Bucais/tratamento farmacológico , Aspirina/farmacologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Celecoxib/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quimiocinas/genética , Citocinas/genética , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/patologia
20.
Toxicol Lett ; 312: 109-117, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31048000

RESUMO

Sulfur mustard (SM) is a highly toxic chemical warfare agent, which produces blisters after skin contact. Treatment of SM-induced adverse health effects, such as cutaneous blistering, ulceration, and inflammation remains a challenging task. Antidotes or specific therapeutic measures are lacking. Some drugs (e.g. cyclooxygenase (COX) inhibitors) exhibited beneficial effects after SM poisoning in vivo. However, in vitro studies that evaluate and compare the potency of COX inhibitors are missing. In the presented study, non-specific (acetylsalicylic acid, ibuprofen, diclofenac, indomethacin, and piroxicam), COX-2-specific (celecoxib and parecoxib) inhibitors and COX-independent drugs (paracetamol and tofacitinib) were compared regarding anti-inflammatory and cytoprotective effects after SM exposure in post-exposure treatment settings. Normal human epidermal keratinocytes (NHEK) were used as a surrogate model. Prostaglandin E2 (PGE2) formation, a direct indicator for COX activity, was determined by ELISA. Changes in pro-inflammatory cytokine levels after SM exposures were assessed by quantitative determination of 27 inflammatory cytokines using a multiplex method. Cytotoxicity was determined using an XTT viability assay. The results demonstrated that SM highly increased PGE2 production and release of pro-inflammatory cytokines, predominantly IL-6, IL-8 and TNF-α. In general, all COX inhibitors and paracetamol were able to reduce the PGE2 formation, while tofacitinib, an inhibitor of Janus kinase, had no influence on PGE2 levels. In addition, IL-6, IL-8, and TNF-α formation were also inhibited, but sometimes independently of PGE2. The COX-2 specific celecoxib was identified as the most potent drug to reduce IL-6, IL-8 and TNF-α formation after SM exposures in vitro. However, cell viability was not improved significantly by any of the investigated drugs in our experiments.


Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Citocinas/metabolismo , Inflamação/induzido quimicamente , Queratinócitos/efeitos dos fármacos , Gás de Mostarda/toxicidade , Linhagem Celular , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/metabolismo
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