Rhinovirus C15 induces airway hyperresponsiveness via calcium mobilization in airway smooth muscle

Vishal Parikh, Jacqueline Scala, Riva Patel, Corinne Corbi, Dennis Lo, Yury A. Bochkov, Joshua L. Kennedy, Richard C. Kurten, Stephen B. Liggett, James E. Gern, Cynthia J. Koziol-White

Research output: Contribution to journalArticlepeer-review

Abstract

Rhinovirus (RV) exposure evokes exacerbations of asthma that markedly impact morbidity and mortality worldwide. The mechanisms by which RV induces airway hyperresponsiveness (AHR) or by which specific RV serotypes differentially evoke AHR remain unknown. We posit that RV infection evokes AHR and inflammatory mediator release, which correlate with degrees of RV infection. Furthermore, we posit that rhinovirus C-induced AHR requires paracrine or autocrine mediator release from epithelium that modulates agonist-induced calcium mobilization in human airway smooth muscle. In these studies, we used an ex vivo model to measure bronchoconstriction and mediator release from infected airways in human precision cut lung slices to understand how RV exposure alters airway constriction. We found that rhinovirus C15 (RV-C15) infection augmented carbachol-induced airway narrowing and significantly increased release of IP-10 (IFN-g-induced protein 10) and MIP-1b (macrophage inflammatory protein-1b) but not IL-6. RV-C15 infection of human airway epithelial cells augmented agonist-induced intracellular calcium flux and phosphorylation of myosin light chain in co-cultured human airway smooth muscle to carbachol, but not after histamine stimulation. Our data suggest that RV-C15-induced structural cell inflammatory responses are associated with viral load but that inflammatory responses and alterations in agonist-mediated constriction of human small airways are uncoupled from viral load of the tissue.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume62
Issue number3
DOIs
StatePublished - Mar 1 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Keywords

  • Asthma
  • Bronchitis
  • Exacerbations
  • Rhinovirus
  • Wheezing

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