RESUMO
Ulcerative colitis (UC) was a nonspecific inflammatory disease. The treatment of UC is imperative. The present study aimed to investigate the effect of nigeglanine on dextran sulfate sodium-induced UC in experimental mice and Caco-2 cells and define the underlying mechanism. The nigeglanine was shown a significant protective effect on the colon, significantly reduced the weight and colon length loss and inhibited intestinal epithelial cell damage. Nigeglanine also reduced proinflammatory factors and increased anti-inflammatory factor production. The results indicate that nigeglanine suppresses the nuclear factor kappa B and mitogen-activated protein kinases pathways in addition to NLRP3 inflammasome action, inhibiting colon epithelial cell pyroptosis. Surprisingly, ZO-1 and occludin protein levels increased with nigeglanine treatment, suggesting that nigeglanine plays a protective role in barrier integrity, reducing colitis progression. The present study suggests that dietary therapy with nigeglanine may be a useful treatment for prophylaxis and palliative UC.
Assuntos
Anti-Inflamatórios/farmacologia , Colite/prevenção & controle , Colo/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Indazóis/farmacologia , Piroptose/efeitos dos fármacos , Animais , Células CACO-2 , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologiaRESUMO
Selenium (Se) is one of the essential trace elements for immune regulation and antioxidant systems in fish growth. The dietary Se plays an important role in immune regulation and inflammation by regulating HSPs and TLRs in liver of many animals. The liver is an important digestive organ in carp. Liver damage can seriously affect the growth and survival of carp. This study was conducted to determine whether Se regulated liver inflammation by affecting HSPs-TLR2 signalling and the potential mechanisms of action in common carp. The gene was analysed by qPCR. The proteins of inflammatory factors were detected by ELISA. The others proteins were analysed by Western blot. The results indicated the Se concentrations in blood and liver tissues were significantly influenced by dietary Se. The Se deficiency increased the expression of HSP60 and TLR2 and the secretion of the proinflammatory factor TNF-α, IL-1ß and IL-6, induced a low secretion of the anti-inflammatory TGF-ß, but the Se supplements could transform these events. Further research showed that with the dose-dependently decrease of Se, the HSP60 expressions were increased, and the MAPKs pathway were significantly activated by the phosphorylation of p38, JNK and ERK in liver tissue and cell. The results provide evidence that Se deficiency induced and exacerbated inflammatory injury to the liver through the HSP60 and TLR2-MAPKs signalling pathways in carp.
Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Imunidade Inata/efeitos dos fármacos , Selênio/metabolismo , Ração Animal/análise , Animais , Chaperonina 60/genética , Chaperonina 60/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/veterinária , Fígado/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Distribuição Aleatória , Selênio/administração & dosagem , Selênio/deficiência , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismoRESUMO
Selenium (Se) is a necessity in multiple species of fish. Se plays an important role in immunoregulation, inflammation, and antioxidant systems in fish and other animals. The head kidney is the major immune organ in adult carp, and it produces white blood cells and destroys old red blood cells. The present study aimed to explore the effects and regulatory molecular mechanisms of Se on ROS and micRNA-146a as part of the inflammatory response in fancy carp. Adult fancy carp were fed different concentrations of Se in their diets. The Se content of the head kidney changed in a pattern consistent with the dietary content of Se. Se deficiency induced a significant increase in ROS, restrained the activities of GPx, SOD and CAT and increased MDA content. qPCR analysis showed a reduction in micRNA-146a with Se deficiency. The Se content, miRNA-146a expression and ROS levels were correlated. H2O2 cell stimulation assays found that ROS could activate the MAPK pathway, and ELISA results showed p38, JNK and ERK phosphorylation significantly increased with H2O2 stimulation. TNF-α, IL-1ß, and IL-6 were appreciably increased. At same time, miRNA-146a, which should have increased to regulate the inflammatory response, was reduced with Se deficiency. Therefore, with Se deficiency, the head kidney was inflamed. All these results indicated that Se deficiency inhibits micRNA-146a to promote ROS-induced inflammation via regulating the MAPK pathway in the head kidney of carp. The present study revealed that supplementing the diet of carp with selenium is beneficial for growth and disease prevention.