Intracellular network of phosphatidylinositol 3-kinase, mammalian target of the rapamycin/70 kDa ribosomal S6 kinase 1, and mitogen-activated protein kinases pathways for regulating mycobacteria-induced IL-23 expression in human macrophages.

摘要: We previously demonstrated that Mycobacterium tuberculosis (M. tbc)-induced interleukin (IL)-12 expression is negatively regulated by the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) 1/2 pathways in human monocyte-derived macrophages (MDMs). To extend these studies, we examined nature of involvement toll-like receptors (TLRs) intracellular signalling downstream from PI3K M. tbc-induced IL-23 MDMs. Akt activation were essentially dependent on TLR2. Blockade mammalian targets rapamycin (mTOR)/70 kDa ribosomal S6 1 (S6K1) pathway specific inhibitor greatly enhanced IL-12/IL-23 p40 (p40) p19 (p19) mRNA protein expression. In sharp contrast, p38 mitogen-activated (MAPK) inhibition abrogated induced tbc. Furthermore, PI3K-Akt, but not ERK pathway, attenuated S6K1 phosphorylation, whereas phosphorylation apoptosis signal-regulating activity during exposure to Although negative or positive regulation was reversed neutralization IL-10, it significantly modulated blocking Collectively, findings provide new insight into homeostatic mechanism controlling type immune responses mycobacterial infection involving network PI3K, S6K1, MAPK a TLR2-dependent manner.