Baicalein regulates NEDD4L-mediated TLR2 ubiquitination to relieve Mycobacterium tuberculosis-induced pneumonia in mice

• Published in: Ciência e tecnologia de alimentos 2022-01, Vol.42
• Main Authors: SHI, Min, YIN, Pengyi, GUO, Xiaobo, LI, Qian, SUN, Lin, CAO, Xiaohua
• Format: Article
• Language: English
• Subjects: FOOD SCIENCE & TECHNOLOGY
• ISSN: 0101-2061; 1678-457X; 1678-457X
• DOI: 10.1590/fst.54321

Abstract Baicalein has strong anti-inflammatory activity, but its efficacy and mechanism in pneumonia of mice is still unclear. Herein, RAW264.7 cells were infected with M. tuberculosis H37Rv (MOI 1:10) after pre-incubation with 50 μM baicalein, and the result found that baicalein incubation ameliorated the increase of bacterial load, and reduced the levels of ROS, IL-12p40, TLR2 protein, phosphorylated JNK protein and M1 polarization markers (iNOS and CD11c), and increased the levels of IL-10, M2 polarization markers (Arg1, Mrc1 and CD206) and NEDD4L protein in H37Rv infected-RAW264.7 cells. And lentivirus-mediated NEDD4L overexpression vector (LV-NEDD4L) transfection had the same effect as baicalein, while small interfering RNA target NEDD4L (si-NEDD4L) transfection or JNK pathway inhibitor IQ 3 treatment reversed the effects of baicalein, and ubiquitin inhibitor MG132 treatment reversed the effects of LV-NEDD4L. Co-immunoprecipitation (Co-IP) and TLR2 ubiquitination assays found that the binding of NEDD4L and TLR2 promoted the ubiquitination of TLR2. In vivo, C57BL/6 mice were nasal infected with H37Rv (1000 ± 150 CFU/mouse) to establish a mouse pneumonia model, and then administered with baicalein. The result found that baicalein improved H37Rv-induced pneumonia in mice. In conclusion, baicalein increased NEDD4L-mediated ubiquitination of TLR2, promoting macrophage M2 polarization and alleviating H37Rv-induced pneumonia.