Investigation on molecular mechanism of angiotension II induced inflammatory activation of pancreatic stellate cells
- VernacularTitle:血管紧张素Ⅱ诱导胰腺星状细胞炎性活化的分子机制研究
- Author:
Lin LU
;
Zhaoshen LI
;
Guoming XU
- Publication Type:Journal Article
- Keywords:
Angiotensin II;
Pancreatic stellate cells;
Nuclear factor-kappaB;
Monocyte chemoat-tractant protein-1
- From:
Chinese Journal of Digestion
2001;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of angiotension II (Ang II ) on the activation of nuclear factor-kappaB (NF-?B) signaling transduction pathway in cultured rat pancreatic stellate cells (PSCs). Methods Growth-arrested rat PSCs were incuhated for indicted time intervals with increasing concentrations of Ang II . The DNA binding activity of NF-?B was determined using electrophoretic mobility shift assay (EMSA). Western blot analysis was used to examine the degradation of inhibitory proteins of NF-?B (I?Bs). Expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein were assessed by Northern blot and enzyme-linked immunosorbent assay (ELISA), respectively. Results Treatment of cells with Ang II led to a biphasic activation of NF-?B, which peaked at 15 min and 6 h later, and it was correlated with differential degradation of I?B? and I?B?. Ang II -induced NF-?B activation was greatly inhibited by antioxidants pyrrolidine dithiocarbamate ( PDTC), diphenylene iodonium. and N-acetylcysteine, suggesting the involvement of oxidative stress in this process. In PSCs, Ang II induced a dose-dependent increase in the expression of MCP-1 and this effect was markedly inhibited by blocking NF-?B activation with MG132 and PDTC, indicating that Ang II -induced MCP-1 gene expression was NF-?B-dependent. Conclusion The present results suggest that Ang II , through an oxidative stress-dependent mechanism, may activate a functional NF-?B signaling pathway in PSCs, through which it may participate in pancreatic inflammation and fibrosis.
