title: 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.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Yen
authors.initials: WY
authors.lastname: Hsu
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chao
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Tsai
authors.forename: Chih-Chan
authors.initials: CC
authors.lastname: Lien
authors.forename: Chao-Fu
authors.initials: CF
authors.lastname: Chang
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Deng
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
authors.forename: Ching Fai
authors.initials: CF
authors.lastname: Kwok
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Juan
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D052243:Resistin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole