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Pulmonary expression and regulation of Cldn6 by tobacco smoke (834.3)
Author(s) -
Jimenez Felix,
Lewis Josh,
Belgique Samuel,
Wood Tyler,
Reynolds Paul
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.834.3
Subject(s) - claudin , copd , tobacco smoke , lung , paracellular transport , respiratory epithelium , a549 cell , immunofluorescence , smoke , tight junction , inflammation , parenchyma , pathology , immunology , epithelium , biology , medicine , microbiology and biotechnology , chemistry , genetics , antibody , environmental health , organic chemistry , membrane , permeability (electromagnetism)
Smoking is a major risk factor for several chronic diseases including chronic obstructive pulmonary disease (COPD), a condition involving both emphysema and inflammation of the airways. COPD severity directly relates to abnormalities of pulmonary epithelial cells. Claudins contribute to tight junctions that prevent paracellular transport of extracellular fluid and diverse substances and Claudin 6 (Cldn6) is a protein expressed prominently in the lung parenchyma. To determine whether Cldn6 was differentially influenced by tobacco smoke, Cldn6 was evaluated by q‐PCR, immunoblitting, and immunofluorescence following exposure to tobacco smoke. Q‐PCR and immunoblotting revealed that Cldn6 was increased in alveolar type II‐like epithelial cells (A549) but not in Bease2B cells, a cell line derived from proximal airway epithelium. Luciferase assays incorporating 0.5kb, 1.0kb, or 2.0kb of the Cldn6 promoter also revealed increased transcription of the gene when cells were exposed to cigarette smoke extract. Cldn6 was also markedly increased in the lungs of Balb/C mice exposed to tobacco smoke delivered by an automated smoke machine (InExpose, Scireq, Canada) compared to animals exposed to room air. These data reveal for the first time that tight junctional proteins are differentially regulated by tobacco smoke exposure and that Cldns are potentially involved as neighboring epithelial cells respond to tobacco smoke. Further research may show that complexes between cells contribute to impaired structural integrity of the lung coincident with smoking. Grant Funding Source : Supported by the Flight Attendant’s Medical Research Institute (FAMRI) and a BYU MEG Award (PRR).