Alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection

Azzeddine Dakhama, Jung Won Park, Christian Taube, Mohamed El Gazzar, Taku Kodama, Nobuaki Miyahara, Katsuyuki Takeda, Arihiko Kanehiro, Annette Balhorn, Anthony Joetham, Joan E. Loader, Gary L. Larsen, Erwin W. Gelfand

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The mechanisms by which respiratory syncytial virus (RSV) infection causes airway hyperresponsiveness (AHR) are not fully established. We hypothesized that RSV infection may alter the expression of airway sensory neuropeptides, thereby contributing to the development of altered airway function. BALB/c mice were infected with RSV followed by assessment of airway function, inflammation, and sensory neuropeptide expression. After RSV infection, mice developed significant airway inflammation associated with increased airway resistance to inhaled methacholine and increased tracheal smooth muscle responsiveness to electrical field stimulation. In these animals, substance P expression was markedly increased, whereas calcitonin gene-related peptide (CGRP) expression was decreased in airway tissue. Prophylactic treatment with Sendide, a highly selective antagonist of the neurokinin-1 receptor, or CGRP, but not the CGRP antagonist CGRP(8-37), inhibited the development of airway inflammation and AHR in RSV-infected animals. Therapeutic treatment with CGRP, but not CGRP(8-37) or Sendide, abolished AHR in RSV-infected animals despite increased substance P levels and previously established airway inflammation. These data suggest that RSV-induced airway dysfunction is, at least in part, due to an imbalance in sensory neuropeptide expression in the airways. Restoration of this balance may be beneficial for the treatment of RSV-mediated airway dysfunction.

Original languageEnglish
Pages (from-to)L761-L770
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume288
Issue number4 32-4
DOIs
Publication statusPublished - 2005 Apr 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection'. Together they form a unique fingerprint.

  • Cite this

    Dakhama, A., Park, J. W., Taube, C., El Gazzar, M., Kodama, T., Miyahara, N., Takeda, K., Kanehiro, A., Balhorn, A., Joetham, A., Loader, J. E., Larsen, G. L., & Gelfand, E. W. (2005). Alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection. American Journal of Physiology - Lung Cellular and Molecular Physiology, 288(4 32-4), L761-L770. https://doi.org/10.1152/ajplung.00143.2004