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

• Autor(a) principal: SHI,Min
• Data de Publicação: 2022
• Outros Autores: YIN,Pengyi, GUO,Xiaobo, LI,Qian, SUN,Lin, CAO,Xiaohua
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Food Science and Technology (Campinas)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0101-20612022000100751
• topic: Mycobacterium tuberculosis; baicalein; NEDD4L; TLR2; pneumonia

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.