Abstract

Cigarette smoke exposure is a major health hazard. Ciliated cells in the epithelium of the airway play a critical role in protection against the noxious effects of inhaled cigarette smoke. Ciliated cell numbers are reduced in smokers which weakens host defense and leads to disease. The mechanisms for the loss of ciliated cells are not well understood. The effects of whole cigarette smoke exposure on human airway ciliated ciliated cells were examined using in vitro cultures of normal human bronchial epithelial cells and a Vitrocell® VC 10® Smoking Robot. These experiments showed that whole cigarette smoke causes the loss of differentiated ciliated cells and inhibits differentiation of ciliated cells from undifferentiated basal cells. Furthermore, treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, Gefitinib, during smoke exposure prevents ciliated cell loss and promotes ciliated cell differentiation from basal cells. Finally, restoration of ciliated cells was inhibited after smoke exposure was ceased but was enhanced by Gefitinib treatment. These data suggest that inhibition of EGFR activity may provide therapeutic benefit for treating smoke related diseases.

Highlights

  • Cigarette smoke exposure is a major cause of death and disease

  • Whole cigarette smoke exposure causes a reduction of ciliated cells in differentiated Normal human bronchial epithelial (NHBE) cells

  • The mRNA levels of two ciliated cell specific genes, FoxJ1 and MCIDAS were significantly reduced in whole cigarette smoke (WCS) treated cells (Fig 1F and 1G). These data suggested that exposure to WCS three times over a seven day period caused an acute reduction in the number of ciliated cells by reducing the expression of MCIDAS and FoxJ1, two genes that are required for ciliogenesis [17, 18]

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Summary

Introduction

Cigarette smoke exposure is a major cause of death and disease. In the United States, more than 480,000 deaths per year are attributable to cigarette smoking. Cigarette smoking is a significant risk factor in a variety of lung diseases including chronic obstructive pulmonary disease (COPD), as well as cardiovascular disease and many cancers. Despite the strong relationships of cigarette smoke and these diseases, the mechanisms by which cigarette smoke causes them are not completely understood [1]. The epithelial cells that line the airway provide the primary barrier between the internal tissues of the body and the inhaled tobacco smoke. As a result of their location, these cells are exposed to the highest smoke levels and are at the greatest risk for cellular damage

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