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Báo cáo y học: " Cytosolic group IVa phospholipase A2 mediates IL-8/CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Cytosolic group IVa phospholipase A2 mediates IL-8/CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro | Meliton et al. Journal of Inflammation 2010 7 14 http www.journal-inflammation.eom content 7 1 14 JOURNAL OF INFLAMMATION RESEARCH Open Access Cytosolic group IVa phospholipase A2 mediates IL-8 CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro Angelo Y Meliton 1 Nilda M Munoz 1 Lucille N Meliton1 David C Binder1 Christopher M Osan1 Xiangdong Zhu1 Steven M Dudek1 and Alan R Leff1 2 Abstract Background Cytosolic gIVaPLA2 is a critical enzyme in the generation of arachidonate metabolites and in induction of P2-integrin adhesion in granulocytes. We hypothesized that gIVaPLA2 activation also is an essential downstream step for post adhesive migration of PMN in vitro. Methods Migration of PMNs caused by IL-8 CXCL8 was assessed using a transwell migration chamber. PMNs were pretreated with two structurally unrelated inhibitors of gIVaPLA2 arachidonyl trifluoromethylketone TFMK or pyrrophenone prior to IL-8 CXCL8 exposure. The fraction of migrated PMNs present in the lower chamber was measured as total myeloperoxidase content. GIVaPLA2 enzyme activity was analyzed using 14C-PAPC as specific substrate F-actin polymerization and cell structure were examined after rhodamine-phalloidin staining. Results IL-8 CXCL8-induced migration of PMNs was elicited in concentration- and time-dependent manner. Time-related phosphorylation and translocation of cytosolic gIVaPLA2 to the nucleus was observed for PMNs stimulated with IL-8 CXCL8 in concentration sufficient to cause upstream phosphorylation of MAPKs ERK-1 2 and p38 and Akt PKB. Inhibition of gIVaPLA2 corresponded to the magnitude of blockade of PMN migration. Neither AA nor LTB4 secretion was elicited following IL-8 CXCL8 activation. In unstimulated PMNs F-actin was located diffusely in the cytosol however a clear polarized morphology with F-actin-rich ruffles around the edges of the cell was observed after activation with IL-8 CXCL8. Inhibition of gIVaPLA2 blocked change in cell shape and migration .