TLR9 Ligands Induce S100A8 in Macrophages via a STAT3-Dependent Pathway which Requires IL-10 and PGE2

摘要: S100A8 and S100A9 are highly-expressed calcium-binding proteins in neutrophils monocytes, subsets of macrophages inflammatory lesions. Unmethylated CpG motifs found bacterial viral DNA potent activators innate immunity via Toll-like receptor 9 (TLR9). S100A8, but not S100A9, mRNA protein was directly induced by CpG-DNA murine human macrophages. Induction peaked at 16 h. CpG-DNA-induced required de novo synthesis; IL-10 Prostaglandin E2 (PGE2) synergistically enhanced expression promoted earlier gene induction. Inhibitors endogenous IL-10, PGE2, the E prostanoid (EP) 4 strongly suppressed expression, particularly when combined. Thus, induction E. coli both PGE2/EP4 signaling. The MAPKs, PI3K JAK pathways were essential, whereas ERK1/2 appeared to play a direct role. controlled transcriptional level. promoter region responsible for activation, either directly, or indirectly located within −178 −34-bp STAT3 binding. Because robust links connecting PGE2 with an anti-inflammatory macrophage phenotype, profile indicates role this resolution inflammation.