Premium
Interleukin‐4 regulates connective tissue growth factor expression in human lung fibroblasts
Author(s) -
Rishikof David C.,
Ricupero Dennis A.,
Kuang PingPing,
Liu Hanqiao,
Goldstein Ronald H.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10144
Subject(s) - ctgf , fibronectin , transforming growth factor , connective tissue , growth factor , microbiology and biotechnology , extracellular matrix , messenger rna , biology , gene expression , transforming growth factor, beta 3 , chemistry , tgf alpha , gene , biochemistry , receptor , genetics
Abstract 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.