中国防痨杂志2024，Vol.46Issue(9)：1063-1068,6.DOI:10.19982/j.issn.1000-6621.20240240
奥布替尼在分枝杆菌感染宿主巨噬细胞中的免疫调控作用
Immunomodulatory effect of orelabrutinib in host macrophages infected with mycobacterium
摘要
Abstract
Objective:To investigate the immunomodulatory effect of a novel Bruton tyrosine kinase(BTK)inhibitor orelabrutinib,in host macrophages infected with Mycobacterium tuberculosis(MTB).Methods:Human acute monocytic leukemia(THP-1)cells were cultured and differentiated.The differentiated THP-1 cells were infected with Mycobacterium smegmatis(M.smeg)and then treated with different concentrations of orelabrutinib to compare the ability of macrophages to engulf and clear M.smeg.BTK protein expression was knocked down by using siRNA interference technology,and the knockdown effect was verified by Western blotting.The colony-forming unit(CFU)assay was used to measure the clearance ability of macrophages against M.smeg by treated with orelabrutinib.Results:Orelabrutinib significantly inhibited the tyrosine phosphorylation of BTK without changing the level of BTK protein expression.Additionally,the CFU count of M.smeg in macrophages treated with orelabrutinib decreased from 130.0(120.3-137.5)× 103/ml to 59.0(55.8-65.3)× 103/ml,with statistical significance(U=0.000,P=0.014).After knocking down BTK protein expression,the bacterial load of M.smeg in macrophages decreased from 52.0(44.0-61.5)× 103/ml to 25.0(22.0-28.0)× 103/ml,with statistical significance(U=9.000,P=0.002).Conclusion:BTK plays a crucial role in macrophage functional regulation.As a novel BTK inhibitor,orelabrutinib not only suppresses BTK tyrosine phosphorylation but also significantly enhances the clearance ability of macrophage against M.smeg,providing a new perspective for its potential anti-tuberculosis applications.关键词
分枝杆菌,结核/蛋白酪氨酸激酶类/巨噬细胞/奥布替尼Key words
Mycobacterium tuberculosis/Protein-tyrosine kinases/Macrophages/Orelabrutinib分类
医药卫生引用本文复制引用
王艺霖,吴潇,逄宇,李姗姗..奥布替尼在分枝杆菌感染宿主巨噬细胞中的免疫调控作用[J].中国防痨杂志,2024,46(9):1063-1068,6.基金项目
National Natural Science Foundation of China(82202530) （82202530）
Beijing Nova Program(20220484169,20230484295) 国家自然科学基金(82202530) （20220484169,20230484295）
北京市科技新星计划创新新星(20220484169、20230484295) （20220484169、20230484295）
