期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 13, 期 7, 页码 1314-1320出版社
WILEY
DOI: 10.1111/j.1582-4934.2008.00529.x
关键词
acinar cells; dexamethasone; MCP-1; N-acetylcysteine; pancreatitis-associated ascitic fluid; signal transduction
资金
- FEDER-FIS (Fondo de Investigacion Sanitaria), Spain [PI05/0025]
Pancreatitis-associated ascitic fluid (PAAF) is known to contribute to the progression of acute pancreatitis (AP). We have investigated the capability of PAAF to activate the expression of MCP-1 in pancreatic acinar cells and the involvement of MAPK, NF-kappa B and STAT3 as downstream signalling transduction pathways. The actions of dexamethasone (Dx) and N-acetylcysteine (NAC) on the PAAF's acinar effects have also been evaluated. Acinar cells were incubated for 1 hr with PAAF collected from rats with severe AP induced by sodium taurocholate in the absence or presence of Dx (10(-7) M) or NAC (30 mM). MCP-1 mRNA expression, phospho-p38-MAPK, I kappa B alpha, nuclear p65 levels and nuclear translocation of STAT3 were analysed. In response to PAAF, overexpression of MCP-1, phosphorylation of p38-MAPK, degradation of I kappa B alpha and increases in p65 nuclear levels and STAT3 activity were found in acinar cells. PAAF-mediated MCP-1 up-regulation was completely suppressed by Dx and NAC. MAPK activation was only inhibited by NAC, NF-kappa B activation was repressed by Dx and NAC, and STAT3 pathway was strongly blocked by Dx and significantly reduced by NAC. In conclusion, acinar cells were activated by PAAF to produce MCP-1, mainly via NF-kappa B and STAT3 pathways. Both downstream pathways were targeted by Dx and NAC to repress the PAAF-mediated acinar MCP-1 up-regulation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据