摘要
目的:探讨2种一线[利福平(RFP)和异烟肼(INH)]和2种二线[阿米卡星(AMK)和对氨基水杨酸(PAS)]抗结核药物对肺泡上皮细胞Toll样受体(TLRs)信号通路信号分子和炎症因子表达的影响。方法:分别采用不同剂量RFP、INH、AMK和PAS作用于A549细胞,qRT-PCR、Western blot和ELISA在核酸和蛋白水平分析TLRs信号通路相关信号分子和炎症因子表达变化。结果:当在细胞培养液中加入10.54μg/ml RFP时,可抑制A549细胞TLRs受体信号通路,降低IL-12表达;当添加5.00μg/ml INH时,可促进NFκB表达及IL-8与IL-12分泌,但TLR2和MyD88表达被抑制;AMK可激活A549细胞TLRs信号通路,并通过其他途径抑制炎症因子IL-8和IL-12表达;PAS可激活A549细胞TLRs信号通路,并促进IL-8、IL-12表达及分泌。结论:RFP和AMK分别抑制和促进TLRs信号通路活化,并抑制炎症因子分泌;INH可激活MyD88非依赖性通路,PAS可活化TLRs信号通路,进而促进炎症因子分泌,为抗结核药物的临床应用提供参考。
Objective:To investigate effect of 2 first-line[rifampicin(RFP)and isoniazid(INH)]and 2 second-line[amikacin(AMK)and para aminosalicylic acid(PAS)]anti-tuberculosis drugs on expressions of signal molecules in alveolar epithelial cells Tollliking receptors(TLRs)signaling pathway and inflammatory factors in A549 cells.Methods:Different concentrations of RFP,INH,AMK and PAS were added into A549 cells respectively.Expressions changes of signal molecules in TLRs signal pathway and inflamma⁃tory factors in nucleic acid and protein levels were detected by qRT-PCR,Western blot and ELISA.Results:TLRs receptor signaling pathway was inhibited and IL-12 expression was reduced when adding 10.54μg/ml RFP in A549 cell medium.Expression of NF-κB was upregulated and secretion of IL-8 and IL-12 was promoted when adding with 5.00μg/ml INF,but TLR2 and MyD88 expressions were downregulated.TLRs signal pathway was activated by AMK,and expressions and secretion of inflammatory factors were inhibited by other pathways.PAS activated TLRS signaling pathway of A549 cells,and promoted expressions and secretions of IL-8 and IL-12.Conclusion:RFP and AMK respectively inhibited and promoted activation of TLRs signaling pathway and inhibited secretion of in⁃flammatory factors.INH can activate MyD88 independent pathway,PAS can activate TLRs signaling pathway and then promoted secre⁃tion of inflammatory factors,which provided reference for clinical application of anti-tuberculosis drugs.
作者
王娟
程龙
李文静
胡育龙
曾瑾
李敏
高蔚丰
李勇
WANG Juan;CHENG Long;LI Wen-Jing;HU Yu-Long;ZENG Jin;LI Min;GAO Wei-Feng;LI Yong(Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China,Ningxia University,Yinchuan 750021,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第6期718-724,共7页
Chinese Journal of Immunology
基金
国家自然科学基金项目(31560694)
宁夏自然科学基金项目(2018AAC03047,NZ17021)。
