The PPE18 Protein of Mycobacterium tuberculosis Inhibits NF-κB/rel-Mediated Proinflammatory Cytokine Production by Upregulating and Phosphorylating Suppressor of Cytokine Signaling 3 Protein

摘要: Mycobacterium tuberculosis bacteria are known to suppress proinflammatory cytokines like IL-12 and TNF-α for a biased Th2 response that favors successful infection its subsequent intracellular survival. However, the signaling pathways targeted by bacilli inhibit production of these not fully understood. In this study, we demonstrate PPE18 protein M. inhibits LPS-induced blocking nuclear translocation p50, p65 NF-κB, c-rel transcription factors. We found upregulates expression as well tyrosine phosphorylation suppressor cytokine 3 (SOCS3), phosphorylated SOCS3 physically interacts with IκBα–NF-κB/rel complex, inhibiting IκBα at serine 32/36 residues IκB kinase-β, thereby prevents NF-κB/rel subunits in LPS-activated macrophages. Specific knockdown small interfering RNA enhanced phosphorylation, leading increased levels factors vis-a-vis p40 macrophages cotreated LPS. The did affect kinase-β activity. Our study describes novel mechanism which NF-κB activation masking site IκBα. Also, highlights possible mechanisms suppresses using PPE18.