Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta

Am J Respir Cell Mol Biol. 2005 May;32(5):470-7. doi: 10.1165/rcmb.2004-0205OC. Epub 2005 Jan 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Anthracenes / metabolism
  • Cells, Cultured
  • Enzyme Activation
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Humans
  • Interleukin-1 / metabolism
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / physiology
  • Middle Aged
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / metabolism
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology*


  • Anthracenes
  • FGF7 protein, human
  • Interleukin-1
  • Proto-Oncogene Proteins c-jun
  • Fibroblast Growth Factor 7
  • pyrazolanthrone
  • Fibroblast Growth Factors
  • JNK Mitogen-Activated Protein Kinases