Abstract

Gap junction channels formed with connexins directly link to the cytoplasm of adjacent cells and have been implicated in intercellular signaling. Connexin 37 (Cx37) is expressed in the gas-exchange region of the lung. Recently, Cx37 has been reported to be involved in the pathogenesis of inflammatory disease. However, no data are available on the role of Cx37 in allergic airway inflammatory disease. In the present study, we used a murine model of ovalbumin (OVA)- induced allergic airway disease and primary murine epithelial cells to examine the change of Cx37 in allergic airway disease. These mice develop the following typical pathophysiological features of asthma: airway hyperresponsiveness, airway inflammation, and increased IL-4, IL-5, IL-13, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, eotaxin, and RANTES levels in lungs. Cx37 protein and mRNA expression were decreased in OVA-induced allergic airway disease. Immunoreactive Cx37 localized in epithelial layers around the bronchioles in control mice, which dramatically disappeared in allergen-induced asthmatic lungs. Moreover, the levels of Cx37 protein in lung tissues showed significantly negative correlations with airway inflammation, airway responsiveness, and levels of Th2 cytokines in lungs. These findings indicate that change of Cx37 may be associated with the asthma phenotype.

Highlights

  • Connexins (Cxs), connexons, and gap junctions are involved in numerous processes contributing to the maintenance of normal cell growth and differentiation (Saez et al, 2003; Jiang and Gu, 2005)

  • The gap junction channels formed with Cxs directly link to the cytoplasm of adjacent cells and have been implicated in intercellular signaling that may regulate the functions of cells

  • We used ovalbumin (OVA)inhaled mice to examine the change of Connexin 37 (Cx37) in allergic airway disease, and we evaluated whether Cx37 is expressed in airway epithelial cells

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Summary

Introduction

Connexins (Cxs), connexons, and gap junctions are involved in numerous processes contributing to the maintenance of normal cell growth and differentiation (Saez et al, 2003; Jiang and Gu, 2005). Cx37 has been reported to play a role in the pathogenesis of various inflammatory diseases (Wagenaar et al, 2004; Chanson and Kwak, 2007). The inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough at night and/or early morning. These symptoms are usually associated with widespread but variable airflow obstruction that is at least partly reversible either spontaneously or with treatment. No data are available on the role of Cx37 in pathogenesis of allergic airway inflammatory disease and the precise localization of Cx37 has not been fully determined in lungs

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