| First Author | Bulek K | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 5 | Pages | 1540-1548 |
| PubMed ID | 30683702 | Mgi Jnum | J:272898 |
| Mgi Id | MGI:6280753 | Doi | 10.4049/jimmunol.1801025 |
| Citation | Bulek K, et al. (2019) IL-17A Recruits Rab35 to IL-17R to Mediate PKCalpha-Dependent Stress Fiber Formation and Airway Smooth Muscle Contractility. J Immunol 202(5):1540-1548 |
| abstractText | IL-17A is a critical proinflammatory cytokine for the pathogenesis of asthma including neutrophilic pulmonary inflammation and airway hyperresponsiveness. In this study, by cell type-specific deletion of IL-17R and adaptor Act1, we demonstrated that IL-17R/Act1 exerts a direct impact on the contraction of airway smooth muscle cells (ASMCs). Mechanistically, IL-17A induced the recruitment of Rab35 (a small monomeric GTPase) and DennD1C (guanine nucleotide exchange factor [GEF]) to the IL-17R/Act1 complex in ASMCs, resulting in activation of Rab35. Rab35 knockdown showed that IL-17A-induced Rab35 activation was essential for protein kinase Calpha (PKCalpha) activation and phosphorylation of fascin at Ser39 in ASMCs, allowing F-actin to interact with myosin to form stress fibers and enhance the contraction induced by methacholine. PKCalpha inhibitor or Rab35 knockdown indeed substantially reduced IL-17A-induced stress fiber formation in ASMCs and attenuated IL-17A-enhanced, methacholine-induced contraction of airway smooth muscle. Taken together, these data indicate that IL-17A promotes airway smooth muscle contraction via direct recruitment of Rab35 to IL-17R, followed by PKCalpha activation and stress fiber formation. |
