摘要
目的支气管平滑肌对气道收缩剂的高反应性是哮喘的主要病理表现,但这种现象背后的分子机制尚未明确。肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的释放对气道高反应性的发生起重要作用。研究旨在考察促炎性细胞因子TNF-α和IL-1β对缓激肽、内皮素-1和血栓素A2的G蛋白偶联受体(GPCR)在人支气管平滑肌细胞(HBSMCs)中mRNA水平的影响。方法将HBSMCs与炎性细胞因子TNF-α,IL-1β,IL-6,IL-13以及MAPK信号通路抑制剂共同培养后,检测缓激肽受体B1和B2、内皮素B受体、血栓素A2受体和β2肾上腺素受体mRNA水平的变化。结果 TNF-α增加了HBSMCs中缓激肽B1和B2受体的mRNA水平,IL-1β增加了HBSMCs中的内皮素B受体的mRNA水平。P38 MAPK抑制剂SB203580和JNK抑制剂SP600125降低了TNF-α上调的缓激肽受体mRNA水平,MEK1/2抑制剂U0126和IκB激酶抑制剂TPCA-1消除了由IL-1β引起的内皮素B受体的mRNA水平增加。结论 TNF-α通过p38 MAPK和JNK信号通路在转录水平上调缓激肽B1和B2受体,IL-1β通过MEK1/2和下游NF-κB通路在转录水平上调HBSMCs中内皮素B受体。
Objective The molecular mechanisms behind airway-hyperresponsiveness to bronchoconstrictor are not fully understood.Release of tumor necrosis factor-alpha（TNF-α）and interleukin-1 beta（IL-1β）during the inflammatory process is believed to play an important role in airway hyperresponsiveness.In the present study,the effects of pro-inflammatory cytokines TNF-αand IL-1βon the G-protein coupled receptors（GPCRs）mRNA for bradykinin,endothelin-1 and thromboxane A2 in human airway smooth muscle cells（HBSMCs）were investigated.Methods Human bronchial smooth muscle cells（HBSMCs）were treated with TNF-α,IL-1β,IL-6,IL-13 and MAPK signaling pathway inhibitors,then bradykinin receptor B1 and B2,endothelin type B receptor,thromboxane A2 receptor andβ2-adrenoceptor mRNA was investigated.Results Bradykinin B1 and B2 receptor mRNA was increased by TNF-αand endothelin type B receptor mRNA was increased by IL-1βin HBSMCs.P38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 attenuated the TNF-αenhanced bradykinin receptors mRNA and MEK1/2 inhibitor U0126 and IκB kinase inhibitor TPCA-1 abrogated the IL-1βenhanced endothelin type B receptor mRNA.Conclusion TNF-αtranscriptionally upregulates bradykinin B1 and B2 receptors via p38 MAPK and JNK signaling pathway and IL-1βtranscriptionally upregulates the endothelin receptor type B via MEK1/2 and the downstream NF-κB pathway in HBSMCs.
作者
蔡艳
杨旭东
雷莹
CAI Yan;YANG Xudong;LEI Ying(Department of Pharmacy,the Second Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710004,China;Department of Biochemistry and Molecular Biology,Health Science Center,Xi′an Jiaotong University,Xi′an 710061,China;BGI-Shenzhen,Shenzhen 518083,China)
出处
《西北药学杂志》
CAS
2018年第3期353-359,共7页
Northwest Pharmaceutical Journal
基金
国家自然科学基金项目(编号:81200001
81603175和81370123)
西安交通大学第二附属医院科研基金项目(编号:YJ(QN)201309)
