LPS-induced expression of the human IL-1 receptor antagonist gene is controlled by multiple interacting promoter elements.

摘要: Expression of the IL-1 receptor antagonist (IL-1ra) can be induced by treatment monocytes and macrophages with LPS. We have previously demonstrated that most proximal 294 bp human IL-1ra promoter are sufficient for full basal activity LPS responsiveness. In present study, we demonstrate presence one inhibitory three positive-acting response elements (LRE) within this 294-bp fragment. By both 5'-deletional analysis heterologous studies, an element between -294 -250 was found to mask response. experiments, two LRE were identified -200 (LRE3) -148 (LRE2) which exhibited cooperativity in neither alone active. Furthermore, LRE2 also cooperated a more site -31 (LRE1), not active alone. LRE1 as NF-kappa B-binding site. Site-directed mutagenesis site, located -93 -84, resulted > 50% decrease responsiveness promoter. electrophoretic mobility shift assays, or without specific antisera members rel/NF-kappa B family, complex binding shown contain primarily B1/p50 lesser amounts RelA/p65. These results indicate net activation involves functional interaction at least four cis-acting DNA bp.