The Regulatory Role Of SOX15 In TLR-mediated Inflammaion Of Macrophages In Response To Mycobacterium Tuberculosis Infection

Background:Tuberculosis is an anthropozoonosis caused by Mycobacterium tuberculosis (Mtb) and alveolar macrophages play a major role against Mtb infection. The proteins encoded by SOX gene family serve as the key transcription factors in developmental biology. The latest study presented the immune regulation effect of SOX genes on inflammatory response, apoptosis and autophagy closely involved in cancers and other diseases. However, the roles and mechanisms of SOX genes in the regulation of immune response of macrophages against Mtb infection have yet elucidated.Methods:qPCR and immunoblotting assays were employed for determination of the alteration of SOX gene expression and Toll-like receptor (TLR) signaling-mediated inflammatory response in human U937 monocyte derived macrophages against an infection of Mtb virulent H37Rv strain.Results:1. An infection of Mtb led an up-regulated expression of SOX B1 subfamily SOX2 and SOX3, SOX F subfamily SOX17 and SOX G subfamily (SOX15) in human U937 monocyte derived macrophages. In addition, an elevated expression of SOX 15 mRNA was also observed in peripheral blood lymphocyte of TB patients, as compared with that of healthy individuals.2. A significantly up-regulated expression of SOX 15 and components of TLR signaling cascade TLR2, TLR4, TLR6, TLR8, TRAF6 and NF-κB was observed in U937 macrophages infected with Mtb H37Rv.3. A strikingly increased expression of inflammatory cytokines IL-1α, IL-2, IL-6, IL-8, IL-12α and TNF-α was observed in U937 macrophages in response to H37Rv infection; and an overexpression of SOX 15 induced an even elevated inflammatory response in macrophages against Mtb infection, alone with activation of TLR signaling and production of inflammatory cytokines.Conclusions:SOX 15 exhibits a pro-inflammatory role in macrophages in response to Mtb infection by regulating the TLR-mediated inflammation.