title: ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells.
abstract: Asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, is also an important inflammatory factor contributing to the development of atherosclerosis (AS). The present study was to test the effect of ADMA on angiotensin (Ang) II-induced monocytic adhesion. Human monocytoid cells (THP-1) or isolated peripheral blood monocyte cells (PBMCs) were incubated with Ang II (10(-6)M) or exogenous ADMA (30 microM) for 4 or 24h in the absence or presence of losartan or antioxidant PDTC. In cultured THP-1 cells, Ang II (10(-6)M) for 24h elevated the level of ADMA in the medium, upregulated the protein expression of protein arginine methyltransferase (PRMT) and decreased the activity of dimethylarginine dimethylaminohydrolase (DDAH). Both of Ang II and ADMA increased monocytic adhesion to human umbilical vein endothelial cells (HUVECs), elevated the levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha and upregulated CCR(2) and CXCR(2) mRNA expression, concomitantly with increase in reactive oxygen species (ROS) generation and activation of nuclear factor (NF)-kappaB. Pretreatment with losartan (10 microM) or PDTC (10 microM) abolished the effects mediated by Ang II or ADMA. In isolated PBMCs from healthy individuals, ADMA upregulated the expression of CXCR(2) mRNA, which was attenuated by losartan (10 microM), however, ADMA had no effect on surface protein expression of CCR(2). The present results suggest that ADMA may be involved in monocytic adhesion induced by Ang II via activation of chemokine receptors by ROS/NF-kappaB pathway.
authors.affiliation: Department of Geriatric Medicine, Xiang-Ya Hospital, Central South University, Xiang-Ya Road 87#, Changsha, Hunan 410008, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Chen
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Li
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bai
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xie
mesh_terms: D000581:Amidohydrolases / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C487735:dimethylarginine; D000804:Angiotensin II; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase