Macrophage inflammatory protein-1 alpha production in lipopolysaccharide-stimulated human adherent blood mononuclear cells is inhibited by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine.

摘要: The release of chemokines such as macrophage-inflammatory protein-1 alpha (MIP-1 alpha) from activated macrophages is a crucial step in cell recruitment necessary for establishing local inflammatory responses. To ascertain the importance L-arginine/nitric oxide (NO) pathway LPS-induced MIP-1 release, we stimulated human adherent PBMC with LPS presence NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). L-NMMA decreased protein (45.5% inhibition) and steady state levels mRNA (48% PBMC. concentration inhibition was dependent on L-arginine culture medium, emphasizing L-arginine-related action drug. Most attributed to activity IL-1 TNF, since coincubation LPS-stimulated IL-1R antagonist TNF-binding abrogated (by 76.8%). Analysis cytokine secretion revealed that, addition alpha, inhibited mature beta 70%) TNF-alpha 53%). In contrast, macrophage chemoattractant unaffected; IL-10 augmented (123.4%) by L-NMMA. exogenous provided donors, enhanced. We concluded that endogenous acts mediator inflammation. Since potent anti-inflammatory cytokine, these data also suggest an agent specifically altering balance pro- cytokines released