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

  • Kim, Jeung-Il (Department of Orthopedic Surgery, Pusan National University Hospital) ;
  • Kim, Hye-Young (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Kim, Sun-Mi (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Lee, Sae-A (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Son, Yong-Hae (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Eo, Seong-Kug (Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Rhim, Byung-Yong (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Kim, Koanhoi (Department of Pharmacology, School of Medicine, Pusan National University)
  • 투고 : 2011.01.17
  • 심사 : 2011.02.19
  • 발행 : 2011.02.28

초록

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 $PSY_1$, $PSY_6$, and $PSY_{11}$ receptors, which all respond to extracellular nucleotides. Exposure of human AoSMCs to $NAD^+$, an agonist of the human $PSY_{11}$ receptor, and $NADP^+$ as well as ATP, an agonist for $PSY_1$ and $PSY_{11}$ 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.

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피인용 문헌

  1. Purinergic Signaling and Blood Vessels in Health and Disease vol.66, pp.1, 2014, https://doi.org/10.1124/pr.113.008029
  2. Preventive effect of nucleoprotein on hindlimb unloading-induced capillary regression in rat soleus muscle vol.89, pp.3, 2014, https://doi.org/10.3109/10520295.2013.835444