Connexin 43 Upregulation in Mouse Lungs during Ovalbumin-Induced Asthma.

Yin Yao,Qing-Xiang Zeng,Xue-Quan Deng,Alicia N Rizzo,Qing-Ling Fu,Guan-Nan Tang,Jie-Bo Guo,Yue-Qi Sun,Kun Ru,Jian-Bo Shi,Christopher Torrens

doi:10.1371/journal.pone.0144106

Abstract

BackgroundConnexin (Cx)-based gap junction channels play important roles in the inflammatory response. Cx43 is involved in the pathogenesis of some lung diseases such as acute lung injury. However, the Cx43 expression in asthma is unclear. In the present study, we used a murine model of ovalbumin (OVA)-induced allergic airway disease to examine the levels of Cx43 and analyze the relationship between Cx43 and airway inflammation in allergic airway disease.MethodsAsthma was induced in mice via sensitization and challenge with OVA. Cx43 mRNA and protein expression levels were investigated via QT-PCR, western blot, and immunohistochemistry 0 h, 8 h, 1 d, 2 d and 4 d after the first challenge. The relationship between Cx43 protein levels and inflammatory cell infiltration, cytokine levels was analyzed.ResultsThe OVA-induced mice exhibited typical pathological features of asthma, including airway hyper-responsiveness; strong inflammatory cell infiltration surrounding the bronchia and vessels; many inflammatory cells in the bronchoalveolar lavage fluid (BALF); higher IL-4, IL-5 and IL-13 levels; and high OVA specific IgE levels. Low Cx43 expression was detected in the lungs of control (PBS) mice. A dramatic increase in the Cx43 mRNA and protein levels was found in the asthmatic mice. Cx43 mRNA and protein expression levels increased in a time-dependent manner in asthma mice, and Cx43 was mostly localized in the alveolar and bronchial epithelial layers. Moreover, lung Cx43 protein levels showed a significant positive correlation with inflammatory cell infiltration in the airway and IL-4 and IL-5 levels in the BALF at different time points after challenge. Interestingly, the increase in Cx43 mRNA and protein levels occurred prior to the appearance of the inflammatory cell infiltration.ConclusionOur data suggest that there is a strong upregulation of Cx43 mRNA and protein levels in the lungs in asthma. Cx43 levels also exhibited a positive correlation with allergic airway inflammation. Cx43 may represent a target to treat allergic airway diseases in the future.

Highlights

Asthma is a common heterogeneous respiratory disease that has increased over the past 50 years [1]
Cx43 mRNA and protein expression levels increased in a time-dependent manner in asthma mice, and Cx43 was mostly localized in the alveolar and bronchial epithelial layers
gap junction channels (GJCs) are essential for coordinating tissue homeostasis and regulating inflammatory responses, which directly link the cytoplasm, which allows for conduction of intercellular signals between adjacent cells

Summary

Introduction

Asthma is a common heterogeneous respiratory disease that has increased over the past 50 years [1]. Despite increasing evidence regarding the import role of epithelial cells in airway allergy inflammation, including contribution of activation and survival of mast cells, basophil and eosinophils [7], the underlying molecular mechanisms remain incompletely characterized, especially regarding the cell-cell interactions and the molecules involved. GJCs are essential for coordinating tissue homeostasis and regulating inflammatory responses, which directly link the cytoplasm, which allows for conduction of intercellular signals between adjacent cells. This behavior enables the lung, which is composed of many types of cells, to behave as an integrated system [11,12,13]. We used a murine model of ovalbumin (OVA)-induced allergic airway disease to examine the levels of Cx43 and analyze the relationship between Cx43 and airway inflammation in allergic airway disease

Methods

Results

Conclusion