tailieunhanh - o cáo hóa học:" Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines | Azari et al. Journal of Translational Medicine 2011 9 98 http content 9 1 98 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines 1 12 3 Bani M Azari Jonathan D Marmur Moro O Salifu Yigal H Ehrlich Elizabeth Kornecki and Anna Babinska 1 Abstract Background - The F11 Receptor F11R aka JAM-A JAM-1 is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells ECs . Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs ensuing with homologous interactions between F11R molecules of platelets and ECs and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the de-novo transcription and translation of F11R molecules induced in ECs by exposure to inflammatory cytokines. Methods - The experimental approach utilized isolated washed human platelet suspensions and cultured human venous endothelial cells HUVEC and human arterial endothelial cells HAEC exposed to the proinflammatory cytokines TNF-alpha and or IFN-gamma for examination of the ability of human platelets to adhere to the inflamed ECs thru the F11R. Our strategy was based on testing the effects of the following inhibitors on this activity general mRNA synthesis inhibitors inhibitors of the NF-kappaB and JAK STAT pathways and small interfering F11R-mRNA siRNAs to specifically silence the F11R gene. Results - Treatment of inflamed ECs with the inhibitors actinomycin parthenolide or with AG-480 resulted in complete blockade of F11R- mRNA expression indicating the involvement of NF-kappaB and JAK STAT pathways in this induction. Transfection of ECs with F11R siRNAs caused complete