巨噬细胞p38丝裂原活化蛋白激酶信号通路促进抗结核菌感染作用  

p38 MAPK activity in macrophages promotes anti-mycobacterium tuberculosis infection

作　　者：盛青[1] 邹威凤[1] 周强[1] 周晓婷[1] 黎希[1] SHENG Qing;ZOU Weifeng;ZHOU Qiang;ZHOU Xiaoting;LI Xi(Department of Respiratory Medicine,Guangzhou Chest Hospital,Guangzhou 510095,China)

机构地区：[1]广州市胸科医院呼吸内科

出　　处：《实用医学杂志》2019年第12期1887-1890,共4页The Journal of Practical Medicine

摘　　要：目的研究p38丝裂原活化蛋白激酶(p38 MAPK)信号通路在抗结核分枝杆菌感染中的作用。方法通过流式细胞仪检测肺组织中p38 MAPK磷酸化水平;蛋白印迹法检测小鼠骨髓来源的巨噬细胞在H37Ra刺激下p38 MAPK的磷酸化水平;用p38 MAPK特异性抑制剂SB203580抑制巨噬细胞中p38MAPK活性后,检测H37Ra感染不同小鼠巨噬细胞后细胞内结核菌的存活率,同时利用qRT-PCR检测H37Ra感染不同小鼠巨噬细胞的细胞因子表达水平。结果 H37Ra雾化的小鼠肺组织中p38 MAPK的磷酸化水平显著高于PBS组(t=5.493,P=0.0006);与空白对照组相比,在H37Ra刺激下,巨噬细胞中p38MAPK的磷酸化水平逐渐增加;用p38 MAPK特异性抑制剂SB203580抑制p38 MAPK活性后,巨噬细胞内H37Ra的存活率显著增加(t=3.674,P=0.0213),H37Ra诱导的巨噬细胞中IL-6(t=9.789、P=0.0006)、TNF-α(t=5.735,P=0.0046)和IL-1β(t=9.311,P=0.0007)的表达水平也明显降低。结论巨噬细胞中p38 MAPK信号通路可能增强机体的抗结核菌感染作用。Objective To study the role of p38 MAPK signaling pathway inanti-mycobacterium tuberculosis infection. Methods Phosphorylation level of p38 MAPK in mouse lung homogenate were measured by flow cytometry. Phosphorylation level of p38 MAPK in mouse bone marrow-derived macrophages(BMDM)stimulated with H37 Ra was detected by Western blotting. After inhibiting the activity of p38 MAPK in macrophages with p38 MAPK specific inhibitor SB203580,the survival rate of mycobacterium tuberculosisin macrophages infected with H37 Ra was detected. Meanwhile,the expression of cytokines in macrophages infected with H37 Ra was detected by qRT-PCR. Results The phosphorylation level of p38 MAPK in H37 Ra-atomized mouse lung homogenate was significantly higher than that in PBS group(t = 5.493,P = 0.0006). Compared with the control group,the phosphorylation level of p38 MAPK in BMDM was increased by H37 Ra infection. The survival of H37 Ra in macrophages was significantly increased after inhibition of p38 MAPK activity by p38 MAPK specific inhibitor SB203580(t = 3.674,P = 0.021 3),and the expression of IL-6(t = 9.789,P = 0.000 6),TNF-α(t = 5.735,P = 0.004 6)and IL-1β(t =9.311,P = 0.000 7)in macrophages infected with H37 Ra were also significantly decreased. Conclusion p38 MAPK signaling pathway in macrophages may enhance the anti-mycobacterium tuberculous effect of macrophages.

关 键 词：P38丝裂原活化蛋白激酶 结核分枝杆菌 结核病 菌落形成单位 骨髓来源的巨噬细胞 

分 类 号：R52[医药卫生—内科学]