Ghrelin inhibits AngII -induced expression of TNF-α IL-8 MCP-1 in human umbilical vein endothelial cells

摘要

Aim: Ghrelin, a gastric peptide, is involved in several metabolic and cardiovascular processes. Emerging evidence indicates the potential involvement of ghrelin in low-grade inflammatory diseases such as atherosclerosis and hypertension. Cytokine-induced inflammation is critical in these pathological states. The growth hormone secretagogue receptor (GHSR) has been identified in blood vessels, so we predict that ghrelin might inhibit proinflammatory responses in human umbilical vein endothelial cells (HUVECs). The aim of this study is to examine the effect of ghrelin on angiotension II (AngII)-induced expression of TNF-α, MCP-1, IL-8 in HUVECs. Method: HUVECs were pretreated with ghrelin, with or without the specific antagonist of GHSR [D-Lys³]-GHRP-6, the selective inhibitor of nuclear factor-kappaB (NF-κB) PDTC, and the selective inhibitor of extracellular signal-regulated kinase (ERK1/2) PD98059. The cells were finally treated with AngII. The expression of TNF-α, MCP-1, IL-8 was examined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The activity of ERK1/2 and NF-κB was analyzed by Western blot. Result: our study showed that ghrelin inhibited AngII -induced expression of IL-8, TNF-α and MCP-1 in the HUVECs via GHSR pathway in concentration- and time-dependent manners. We also found that ghrelin inhibited AngII -induced activation of ERK1/2 and NF-κB. Conclusions: these results suggest that Ghrelin may play novel antiinflammatory and immunoregulatory roles in HUVECs.