Angiotensin-(-) prevents lipopolysaccharide-induced hepatocellular inflammatory response by inhibiting the p38MAPK/AP-1 signaling pathway

The pathological mechanism of lipopolysaccharide (LPS)-induced liver injury involves a number of inflammatory mediators and cytokines. Angiotensin (Ang)-(1-7), a ligand for the proto-oncogene Mas (Mas) receptor, antagonizes the actions of Ang II in the renin angiotensin system and exerts an anti-inflammatory effect on LPS-induced macrophages. The present study investigated the potential role of Ang-(1-7) in the regulation of inflammatory responses in LPS-induced hepatocytes using the rat liver BRL cell line. The results of the present study demonstrated that the inflammatory mediator, tumor necrosis factor (TNF)-, its upstream transcriptional regulatory factor activator protein (AP)-1 and p38 mitogen activated protein kinase (MAPK) which were detected by reverse transcription-quantitative polymerase chain reaction and western blotting were upregulated in LPS-induced hepatic cells in a time-dependent manner, peaking 12 h following LPS stimulation. By contrast, treatment with Ang-(1-7) significantly attenuated the expression of TNF-, AP-1 and p38MAPK in a concentration-dependent manner. The anti-inflammatory effect of Ang-(1-7) was reversed by the Mas receptor selective antagonist, A779, in BRL cells. Furthermore, the p38MAPK inhibitor, SB 203580, abolished the protective effects of Ang-(1-7), suggesting the involvement of the p38MAPK pathway in the anti-inflammatory activity of Ang-(1-7). The results of the present study indicated that Ang-(1-7) may serve an anti-inflammatory role in LPS-induced hepatocyte injury via the regulation of the p38MAPK/AP-1 signaling pathway.