IP-10 Decreases TNF-alpha Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis.
10.4046/trd.2008.64.5.347
- Author:
Seung Joon KIM
1
;
Chun Mi KANG
;
Moon Bin YOU
;
Hyung Kyu YOON
;
Young Kyoon KIM
;
Kwan Hyoung KIM
;
Hwa Sik MOON
;
Sung Hak PARK
;
Jeong Sup SONG
Author Information
1. Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. jssong@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Idiopathic pulmonary fibrosis;
MUC5AC;
IP-10;
Epidermal growth factor receptor;
Mitogen-activated protein kinase
- MeSH:
Carcinoma, Mucoepidermoid;
Cell Line;
Cough;
Dyspnea;
Enzyme-Linked Immunosorbent Assay;
Gene Expression;
Humans;
Idiopathic Pulmonary Fibrosis;
Leukocytes;
Lung;
Lung Diseases;
Mucins;
Mucus;
Receptor, Epidermal Growth Factor;
Signal Transduction;
Sputum;
Tumor Necrosis Factor-alpha
- From:Tuberculosis and Respiratory Diseases
2008;64(5):347-355
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. METHODS: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-alpha with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. RESULTS: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-alpha induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. CONCLUSION: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.
