Abstract
Airway remodeling due to increased airway smooth muscle (ASM) mass, likely due to enhanced migration and proliferation, has been shown to be highly associated with decline in lung function in asthma. Thymic stromal lymphopoietin (TSLP) is an IL-7-like, pro-allergic cytokine that has been shown to be necessary and sufficient for the development of allergic asthma. Human ASM (HASM) cells express TSLP receptor (TSLPR), the activation of which leads to enhanced release of proinflammatory mediators such as IL-6, CCL11/eotaxin-1, and CXCL8/IL-8. We show here that TSLP induces HASM cell migration through STAT3 activation since lentiviral-shRNA inhibition of STAT3 abrogated the TSLP-induced cell migration. Moreover, TSLP induced multiple cytoskeleton changes in HASM cells such as actin polymerization, cell polarization, and activation of small GTPase Rac1. Collectively, our data suggest a pro-migratory function of TSLP in ASM remodeling and provides better rationale for targeting TSLP/TSLPR pathway for therapeutic approaches in allergic asthma.
Highlights
Airway remodeling due to increased airway smooth muscle (ASM) mass, likely due to enhanced migration and proliferation, has been shown to be highly associated with decline in lung function in asthma
We found that the recombinant human Thymic stromal lymphopoietin (TSLP) (1–10 ng/ml) induces Human ASM (HASM) cell migration (p, 0.001, n 5 4, Fig. 1A)
We have previously established that Signal transducer and activator of transcription 3 (STAT3) but not STAT5 is phosphorylated and only STAT3 activation is required for TSLP-induced HASM cell synthetic functions[12]
Summary
Airway remodeling due to increased airway smooth muscle (ASM) mass, likely due to enhanced migration and proliferation, has been shown to be highly associated with decline in lung function in asthma. The source of migrating ASM cells in airways remain a matter of debate (e.g. from circulating fibrocytes, the original deeper ASM layer, or from bone marrow/lung-derived mesenchymal stem cells), the process of migration has been proposed extensively to underlie, at least in part, the airway remodeling and the pathogenesis of asthma[2]. These structural changes are known to cause substantial airflow limitation in asthma[3], they are not reversed by currently availably asthma therapies. For the first time, an increased HASM cell migration in response to TSLP stimulation, and uncover some of the putative signaling mechanisms involved in this process
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
