TNF-α and IL-1βupregulate bradykinin receptors and endothelin receptor in human bronchial smooth muscle cells via MAPK signaling pathways
Objective The molecular mechanisms behind airway-hyperresponsiveness to bronchoconstrictor are not fully understood. Release of tumor necrosis factor-alpha(TNF-α)and interleukin-1beta(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-1β on the G-protein coupled receptors(GPCRs)mRNA for bradykinin,endothelin-1 and thromboxane A2in 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,throm-boxane A2receptor and β2-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 inhibi-tor 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 bradyki-nin 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.
TNF-αIL-1βhuman bronchial smooth muscle cellbradykinin receptorendothelin B receptorMAPK
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