Angiotensin‑(1‑7) 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)‑α, 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‑α, 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.