Interleukin-4 regulates connective tissue growth factor expression in human lung fibroblasts

J Cell Biochem. 2002;85(3):496-504. doi: 10.1002/jcb.10144.

Abstract

Transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) have fibrogenic properties and induce extracellular matrix production in a variety of lung diseases. Connective tissue growth factor (CTGF) is a matrix signaling molecule stimulated by TGF-beta that in part mediates alpha1(I) collagen mRNA expression. In these studies, the regulation of CTGF expression by IL-4 in human lung fibroblasts was examined. Following 6 h of stimulation with IL-4, basal CTGF mRNA levels were unchanged as assessed by Northern blot analysis. However, IL-4 attenuated the TGF-beta-stimulated induction of CTGF mRNA expression by 50%. This effect was selective because IL-4 did not affect fibronectin or alpha1(I) collagen mRNA expression induced by TGF-beta. Experiments employing the transcriptional inhibitor actinomycin D suggest that IL-4 did not affect the stability of the CTGF mRNA. Transient transfection assays with 3TP-Lux, a luciferase gene controlled by a TGF-beta inducible promoter, and with a CTGF promoter construct indicate that IL-4 interfered with the TGF-beta-induced transcriptional activation of the CTGF gene.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Collagen Type I / drug effects
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Connective Tissue Growth Factor
  • Dactinomycin / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibronectins / drug effects
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Immediate-Early Proteins / drug effects
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • Insulin / pharmacology
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-4 / metabolism*
  • Interleukin-4 / pharmacology
  • Lung / cytology
  • Lung / embryology
  • Lung / metabolism*
  • MAP Kinase Kinase Kinase 1*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Promoter Regions, Genetic
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • CCN2 protein, human
  • Collagen Type I
  • Enzyme Inhibitors
  • Fibronectins
  • Immediate-Early Proteins
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • Dactinomycin
  • Interleukin-4
  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human