Lipopolysaccharide-Induced M2 to M1 Macrophage Transformation for IL-12p70 Production Is Blocked by Candida albicans Mediated Up-Regulation of EBI3 Expression

摘要: Macrophages are heterogeneous cell populations that present in all tissues. can be divided into classically activated inflammatory macrophages (M1) and alternatively anti-inflammatory (M2). It has been generally accepted M1 polarised an environment to produce pro-inflammatory cytokines, whilst M2 involved anti-inflammation aid tissue repair wound healing. Bacterial endotoxin (lipopolysaccharide; LPS) is a potent factor infection, which induces resulting higher levels of iNOS, TNFα IL-12p70 dictate T responses. transformed following LPS stimulation promote inflammation. Candida albicans commensal fungal microorganism, suggested induce immune tolerance; however, the mechanism C. albicans-induced tolerance not investigated detail. IL-35 recently identified cytokine heterodimeric protein consisting Epstein-Barr virus-induced gene 3 (EBI3) IL-12p35. shares subunit p35, with IL-12p70. most Th1 responses during In this study, we demonstrate heat-killed (HKC) strongly suppressed LPS-induced production macrophages. induced high level EBI3 expression macrophages, served as for suppression by competitive binding common (p35) To had ability block intracellularly, Chinese Hamster Ovary (CHO) line biscistronic IL-12p40 p35 was constructed, followed ectopic over-expression EBI3. The producing effectively production. secretion also detected line, immune-precipitation Western blotting. However, evident HKC. This explained constitutive receptors (gp130 IL-12Rβ2) consumption. Our results have indicated suppress host mucosal skin suppressing Lower may avoid unnecessary response order retain tolerance, one mechanisms achieves successful lifestyle without having detrimental effect on host's health.