Mycobacterium tuberculosis Rv2185c contributes to nuclear factor-κB activation

Abstract Tuberculosis caused by Mycobacterium tuberculosis has a detrimental impact on public health worldwide, especially in developing countries. The nuclear factor-κB (NF-κB) signaling pathway is reportedly involved in the innate immune response against M. tuberculosis infections. We screened the secreted proteins, membrane proteins, and lipoproteins of the M. tuberculosis H37Rv strain using luciferase activity assays. The Rv2185c protein exhibited the potential to activate NF-κB in HeLa and A549 cells. Overexpression of Rv2185c-induced IκBα degradation and nuclear translocation of NF-κB; it also induced NF-κB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, IL-1β and tumor necrosis factor (TNF)-α. The intact binding site for the NF-κB element is required for the activation of Rv2185c-induced IL-6 and IL-8 gene expression. NF-κB activation and NF-κB-regulated genes encoding TNF-α and TNF-related apoptosis-inducing ligand have also been shown to be involved in Rv2185c-induced apoptosis.