Transcriptional regulation of the rat type IIA phospholipase A2 gene by cAMP and interleukin-1beta in vascular smooth muscle cells: interplay of the CCAAT/enhancer binding protein (C/EBP), nuclear factor-kappaB and Ets transcription factors.

摘要: The abundant secretion of type IIA secreted phospholipase A(2) (sPLA(2)) is a major feature the inflammatory process atherosclerosis. sPLA(2) crucial for development inflammation, as it catalyses production lipid mediators and induces proliferation smooth muscle cells. We have analysed activation transcription by cAMP interleukin-1beta (IL-1beta), shown that 500 bp region upstream start site rat gene implicated in synergistically acting IL-1beta. transiently transfected stimulated cells primary culture measured promoter activities serial site-directed deletion mutants sPLA(2)-luciferase constructs. A distal region, between -488 -157 bp, bearing CAAT/enhancer binding protein (C/EBP)-responsive element (-242 to -223) was sufficient cAMP/protein kinase A-mediated activation. find evidence first time IL-1beta requires an Ets-responsive -184 -180 via Ras pathway nuclear factor-kappaB at positions -141 -131 proximal promoter. also used electrophoretic mobility shift assays identify five sites Sp1 factor; specific inhibitor Sp1, mithramycin A, showed this factor basal activity