Resistin induces monocyte–endothelial cell adhesion by increasing ICAM‐1 and VCAM‐1 expression in endothelial cells via p38MAPK‐dependent pathway

Abstract

Resistin, firstly reported as an adipocyte-specific hormone, is suggested to be an important link between obesity and diabetes. Recent studies have suggested an association between resistin and atherogenic processes. The adhesion of circulating monocytes to endothelial cells is a critical step in the early stages of atherosclerosis. The purpose of the present study was to investigate the effect of resistin on the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Our results showed that resistin caused a significant increase in monocyte adhesion. In exploring the underlying mechanisms of resistin action, we found that resistin-induced monocyte adhesion was blocked by inhibition of p38MAPK activation using SB203580 and SB202190. Furthermore, resistin increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by HUVECs and these effects were also p38MAPK-dependent. Resistin-induced monocyte adhesion was also blocked by monoclonal antibodies against ICAM-1 and VCAM-1. Taken together, these results show that resistin increases both the expression of ICAM-1 and VCAM-1 by endothelial cells and monocyte adhesion to HUVECs via p38MAPK-dependent pathways.

Mechanisms Linking Excess Adiposity and Carcinogenesis Promotion

“…While adipose tissue constitutes the main source of resistin in mice, this molecule is secreted mainly by monocytes and macrophages in humans (217). Human resistin is implicated in the pathogenesis of atherosclerosis by promoting smooth muscle cell proliferation and migration, ICAM-1 and VCAM-1 expression, as well as via regulating patterns of adhesion and inflammation in atherosclerotic plaques (218, 219). Several colorectal cancer studies have shown a positive correlation between resistin and tumor size based on T-staging and tumor grading (172, 220).…”

Human resistin in cardiovascular disease

“…Human recombinant resistin increased the expression of pro-atherogenic molecule, ET-1, VCAM-1 and MCP-1 and down-regulated anti-atherogenic molecule TRAF-3, an inhibitor of CD40 ligand signaling in endothelial cells (Verma et al, 2003). Human resistin was shown to induce adhesion molecule, ICAM-1 and VCAM-1 in endothelial cell and thereby increase monocyte-endothelial cell adhesion (Kawanami et al, 2004;Cho et al, 2011;Hsu et al, 2011). Resistin was expressed by rat vascular smooth muscle cells and it was stimulated by hypoxia or cyclic mechanical stretch (Hung et al, 2008;Wang et al, 2010).…”

ICAM-1 and IL-8 Are Expressed by DEHP and Suppressed by Curcumin Through ERK and p38 MAPK in Human Umbilical Vein Endothelial Cells

“…Several environmental chemicals have been reported to be potential activators for ICAM-1 [19][20][21]. Studies have shown that stimuli-induced upregulation of ICAM-1 in endothelial cells was mediated by the activation of MAPK [16]. However, there is little information on the effect of DEHP on ICAM-1 activity in HUVECs.…”

“…However, the effect of higher concentrations of DEHP (1-25 μM) on the IL-8 expression in HUVECs remains unknown. ICAM-1, an inducible cell transmembrane glycoprotein of the immunoglobulin supergene family, acts as a key component in inflammatory response for recruitment of leukocytes to the sites of inflammation and is implicated in the pathogenesis of numerous inflammatory diseases such as asthma, rheumatoid arthritis, and atherosclerosis [14][15][16][17][18]. Several environmental chemicals have been reported to be potential activators for ICAM-1 [19][20][21].…”