Mechanism of interferon-gamma mediated down-regulation of interleukin-10 gene expression.

Expression of the anti-inflammatory cytokine IL-10 is suppressed by the pro-inflammatory interferon gamma but the mechanism of this action is unknown. We analysed activity of IL-10 promoter luciferase reporter constructs in transfected RPMI 8226.1 B cells that were treated at -2 h with IFNgamma (1000 U/ml) followed by stimulation with LPS (100 ng/ml) at 0 h.

Role of STAT3 in glucocorticoid-induced expression of the human IL-10 gene.

In the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10(-6) M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation.

Stat3 is involved in control of MASP2 gene expression.

Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed.