Baicalein inhibits mycobacterium tuberculosis-induced macrophage M1 polarization depending on the regulation of YY1/RAB10/TLR4 pathway.

BACKGROUND: Baicalein (Bai) has been found to alleviate the progression of tuberculosis (TB) by inhibiting mycobacterium tuberculosis (M.tb)-induced macrophage pyroptosis, so it may be used as an adjuvant treatment for TB. However, the underlying molecular mechanism of Bai remains unclear. METHODS: THP-1 macrophages were infected with M.tb and treated with Bai. The viability and apoptosis of macrophages were examined with CCK8 assay, flow cytometry and TUNEL staining. The levels of inflammatory cytokines were tested by ELISA. Macrophage M1 polarization was assessed by detecting CD86(+) cell rate using flow cytometry. The protein levels of RAB10, YY1, TLR4, MYD88, p-P65/P65 and p-IκBα/IκBα were determined using western blot. The interaction between RAB10 and YY1 or TLR4 was confirmed by ChIP assay, dual-luciferase reporter assay and Co-IP assay. RESULTS: M.tb promoted macrophage M1 polarization, apoptosis and inflammation, while this effect was abolished by Bai treatment. Bai decreased RAB10 expression, and RAB10 overexpression reversed the anti-TB effect of Bai. YY1 enhanced the transcription of RAB10, and YY1 knockdown inhibited M.tb-induced macrophage M1 polarization by reducing RAB10 expression. Also, Bai could decrease YY1 expression, and YY1 overexpression eliminated the regulation of Bai on M.tb-induced macrophage M1 polarization. Moreover, RAB10 could interact with TLR4 to activate TLR4/MYD88/NF-κB pathway, thus promoting M.tb-induced macrophage M1 polarization. CONCLUSION: Bai might play anti-TB effect by regulating YY1/RAB10/TLR4/MYD88/NF-κB pathway, providing a novel idea for the treatment of TB.