Interleukin-17A directly acts on bronchial smooth muscle cells and augments the contractility

Background although interleukin-17 (il-17) contributes to the induction of airway hyperresponsiveness in asthma,its effect on bronchial smooth muscle (bsm) remains largely unknown. evidence support an involvement of rhoa/rho-kinase in bsm contraction,and the pathway has now been proposed as a novel target for asthma therapy. to clarify the role of il-17 on the development of bsm hyperresponsiveness,effects of il-17a on bsm contractility and rhoa expression were investigated. methods male balb/c mice and cultured human bsm cells (hbsmcs) were used. results in the murine model of allergic asthma,bsm hyperresponsiveness with an il-17a up-regulation in bronchoalveolar lavage fluids were observed. rt-pcr analyses revealed the expression of receptors for il-17a in mouse bsms and hbsmcs. in the hbsmcs,incubation with il-17a caused an up-regulation of rhoa protein. western blot analyses also revealed phosphorylations of jnks/erks and a down-regulation of iκb-α in the il-17a-treated hbsmcs,indicating that il-17a could act on bsm cells directly. however,il-17a did not activate stat6,which is also known as a signaling molecule that causes an up-regulation of rhoa when activated by il-13. on the other hand,il-17a caused a down-regulation of mir-133a-3p,a microrna that negatively regulates rhoa translation. in the naive mice,in vivo il-17a treatment to the airways by intranasal instillation induced a bsm hyperresponsiveness with rhoa protein up-regulation. conclusions these findings indicate that il-17 directly acts on bsm cells and up-regulates rhoa protein probably via a down-regulation of mir-133a-3p,resulting in an induction of the bsm hyperresponsiveness. © 2016