Document Detail

Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta.
MedLine Citation:
PMID:  15677771     Owner:  NLM     Status:  MEDLINE    
Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 10) and from control subjects (n = 7) at baseline and after IL-1beta stimulation. Basal KGF secretion by IPF fibroblasts was similar to controls. In fibroblasts from control subjects, IL-1beta increased c-Jun expression, c-Jun activation, and KGF secretion. SP600125, a specific c-Jun N-terminal kinase (JNK) inhibitor, inhibited the effect of IL-1beta. By contrast, in IPF fibroblasts, IL-1beta did not increase c-Jun expression and c-Jun activation, and weakly increased KGF secretion, whereas SP600125 had no effect. IL-1beta similarly increased JunB expression in fibroblasts from patients with IPF and control subjects. Total JNK content was not different in either unstimulated or IL-1beta-stimulated IPF and control fibroblasts. IL-1beta increased phosphorylated JNK in control and IPF fibroblasts, but this increase was weaker and heterogeneous in IPF. Altogether, our results demonstrate a dysregulation of KGF secretion by IPF fibroblasts. The weak response to IL-1beta is associated with a defect of c-Jun expression and activation and a defect of JNK activation.
Sylvain Marchand-Adam; Laurent Plantier; Dominique Bernuau; Agnès Legrand; Murielle Cohen; Joëlle Marchal; Paul Soler; Guy Lesèche; Hervé Mal; Michel Aubier; Monique Dehoux; Bruno Crestani
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-27
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  32     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-19     Completed Date:  2005-06-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  470-7     Citation Subset:  IM    
Service de Pneumologie, Hôpital Bichat, 16 rue Henri Huchard, 75877 Paris cedex 18, France.
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MeSH Terms
Anthracenes / metabolism
Cells, Cultured
Enzyme Activation
Fibroblast Growth Factor 7
Fibroblast Growth Factors / genetics,  metabolism*
Fibroblasts / cytology,  metabolism*
Interleukin-1 / metabolism
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
MAP Kinase Signaling System / physiology
Middle Aged
Proto-Oncogene Proteins c-jun / metabolism
Pulmonary Fibrosis / metabolism,  pathology*
Reg. No./Substance:
0/Anthracenes; 0/FGF7 protein, human; 0/Interleukin-1; 0/Proto-Oncogene Proteins c-jun; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 126469-10-1/Fibroblast Growth Factor 7; 62031-54-3/Fibroblast Growth Factors; EC Mitogen-Activated Protein Kinases

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