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1.
Naunyn Schmiedebergs Arch Pharmacol ; 390(3): 261-268, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27942772

RESUMO

Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis. Next, we ask whether IL-19 contributes to T cells-mediated colitis. Here, we investigated the role of IL-19 in a mouse model of Th2 cell-mediated colitis. Inflammatory responses in IL-19-deficient mice were assessed using a Th2-mediated colitis induced by oxazolone. The colitis was evaluated by analyzing the body weight loss and histology of the colon. Lymph node cells were cultured in vitro to determine cytokine production. IL-19 knockout mice exacerbated oxazolone-induced colitis by stimulating the transport of inflammatory cells into the colon, and by increasing IgE production and the number of circulating eosinophil. The exacerbation of oxazolone-induced colonic inflammation following IL-19 knockout mice was accompanied by an increased production of IL-4 and IL-9, but no changes in the expression of IL-5 and IL-13 in lymph node cells. IL-19 plays an anti-inflammatory role in the Th2-mediated colitis model, suggesting that IL-19 may represent a potential therapeutic target for reducing colonic inflammation.


Assuntos
Colite/prevenção & controle , Colo/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-10/metabolismo , Células Th2/metabolismo , Animais , Células Cultivadas , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/imunologia , Colo/patologia , Modelos Animais de Doenças , Predisposição Genética para Doença , Mediadores da Inflamação/imunologia , Interleucina-10/deficiência , Interleucina-10/genética , Interleucinas , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxazolona , Fenótipo , Fatores de Proteção , Células Th2/imunologia , Fatores de Tempo
2.
Naunyn Schmiedebergs Arch Pharmacol ; 389(10): 1081-90, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27411318

RESUMO

The Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP.


Assuntos
Motilidade Gastrointestinal , Íleo/metabolismo , Contração Muscular , Músculo Liso/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Acetilcolina/farmacologia , Animais , Estimulação Elétrica , Motilidade Gastrointestinal/efeitos dos fármacos , Genótipo , Íleo/efeitos dos fármacos , Íleo/inervação , Técnicas In Vitro , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/inervação , Fenótipo , Trocador de Sódio e Cálcio/genética , Substância P/farmacologia
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