Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease.

Abstract

Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.

• Authors: Isao Nakao, Sachiko Kanaji, Shoichiro Ohta, Hidetomo Matsushita, Kazuhiko Arima, Noriko Yuyama, Mutsuo Yamaya, Katsutoshi Nakayama, Hiroshi Kubo, Mika Watanabe, Hironori Sagara, Kumiya Sugiyama, Hiroyuki Tanaka, Shuji Toda, Hiroaki Hayashi, Hiromasa Inoue, Tomoaki Hoshino, Aya Shiraki, Makoto Inoue, Koichi Suzuki, Hisamichi Aizawa, Satoshi Okinami, Hiroichi Nagai, Mamoru Hasegawa, Takeshi Fukuda, Eric D Green, Kenji Izuhara
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 9 Pg. 6262-9 (May 01 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18424749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-13
• MUC5AC protein, human
• Membrane Transport Proteins
• Muc5ac protein, mouse
• Mucin 5AC
• Mucins
• SLC26A4 protein, human
• Sulfate Transporters

Topics

• Aged
• Animals
• Asthma (genetics, immunology)
• COS Cells
• Chlorocebus aethiops
• Disease Models, Animal
• Epithelial Cells (immunology)
• Female
• Genome, Human (immunology)
• Humans
• Interleukin-13 (immunology)
• Lung (immunology)
• Male
• Membrane Transport Proteins (genetics, immunology)
• Mice
• Middle Aged
• Mucin 5AC
• Mucins (genetics, immunology)
• Mucus (immunology)
• Neutrophil Infiltration (genetics, immunology)
• Neutrophils (immunology)
• Pulmonary Disease, Chronic Obstructive (genetics, immunology)
• Respiratory Mucosa (immunology)
• Sulfate Transporters
• Th2 Cells (immunology)