Extracellular Nucleotides Can Induce Chemokine (C-C motif) Ligand 2 Expression in Human Vascular Smooth Muscle Cells

• Published in: The Korean journal of physiology & pharmacology Vol. 15; no. 1; pp. 31 - 36
• Main Authors: Kim, Jeung-Il, Kim, Hye-Young, Kim, Sun-Mi, Lee, Sae-A, Son, Yong-Hae, Eo, Seong-Kug, Rhim, Byung-Yong, Kim, Koanhoi
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.02.2011; 대한약리학회
• Subjects: Original; 약리학; NAD; CCL2; Vascular smooth muscle cell; P2 receptors
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2011.15.1.31

To understand the roles of purinergic receptors and cellular molecules below the receptors in the vascular inflammatory response, we determined if extracellular nucleotides up-regulated chemokine expression in vascular smooth muscle cells (VSMCs). Human aortic smooth muscle cells (AoSMCs) abundantly express P2Y(1), P2Y(6), and P2Y(11) receptors, which all respond to extracellular nucleotides. Exposure of human AoSMCs to NAD(+), an agonist of the human P2Y(11) receptor, and NADP(+) as well as ATP, an agonist for P2Y(1) and P2Y(11) receptors, caused increase in chemokine (C-C motif) ligand 2 gene (CCL2) transcript and CCL2 release; however, UPT did not affect CCL2 expression. CCL2 release by NAD(+) and NADP(+) was inhibited by a concentration dependent manner by suramin, an antagonist of P2-purinergic receptors. NAD(+) and NADP(+) activated protein kinase C and enhanced phosphorylation of mitogen-activated protein kinases and Akt. NAD(+)- and NADP(+)-mediated CCL2 release was significantly attenuated by SP6001250, U0126, LY294002, Akt inhibitor IV, RO318220, GF109203X, and diphenyleneiodium chloride. These results indicate that extracellular nucleotides can promote the proinflammatory VSMC phenotype by up-regulating CCL2 expression, and that multiple cellular elements, including phosphatidylinositol 3-kinase, Akt, protein kinase C, and mitogen-activated protein kinases, are involved in that process.