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

• Published in: Journal of cellular biochemistry 2002, Vol.85 (3), p.496-504
• Main Authors: Rishikof, David C., Ricupero, Dennis A., Kuang, Ping-Ping, Liu, Hanqiao, Goldstein, Ronald H.
• Format: Article
• Language: English
• Subjects: 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; fibrosis; 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 - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; RNA, Messenger - metabolism; Smad; Stat; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; transforming growth factor-β
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.10144

Transforming growth factor‐β (TGF‐β) 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‐β that in part mediates α1(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‐β‐stimulated induction of CTGF mRNA expression by 50%. This effect was selective because IL‐4 did not affect fibronectin or α1(I) collagen mRNA expression induced by TGF‐β. 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‐β inducible promoter, and with a CTGF promoter construct indicate that IL‐4 interfered with the TGF‐β‐induced transcriptional activation of the CTGF gene. J. Cell. Biochem. 85: 496–504, 2002. © 2002 Wiley‐Liss, Inc.