TFF-3 Modulates Responsiveness to Bronchodilators in Airways

Abstract

Rhinovirus (RV) is the major cause of exacerbations, or worsening of symptoms, in asthmatic children and adults. This often reduces the efficacy of therapeutic interventions such as bronchodilators — a type of medication used to promote airflow and alleviate asthma symptoms. The exact mechanisms through which RV exposure decreases responsiveness to bronchodilators remain unclear. Previous data demonstrates that airway cells release a specific signature of inflammatory mediators following RV exposure. Other research has shown that Trefoil Factor 3 (TFF-3), one of the mediators identified by our screen, regulates cell motility in other cell types. We show that RV exposure attenuates relaxation in both the airway and human airway smooth muscle (HASM). Given our data, we aim to examine whether or not TFF-3 attenuates the relaxation of HASM and airways.

Primary non-diseased human airway smooth muscle (HASM) was used to examine the consequences of TFF-3 in modulating HASM and airway relaxation. Following RV-C15 exposure, it was found that the airway and HASM relaxation was attenuated. TFF-3 exposure also attenuated both airway and HASM relaxation. Additionally, TFF-3 exposure partially weakened iso-induced reversal of carbachol-induced phosphorylation of the myosin light chain. Within the cADDis Live Cell Assays, which provide real-time kinetic measurements of cyclic Adenosine Monophosphate (cAMP) production, TFF-3 attenuated formoterol-induced cAMP production. Researching how bronchodilation pathways change following RV infection can lead to the development of effective treatments and pharmaceutical solutions to alleviate worsening asthma symptoms during a viral exacerbation of the disease.