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

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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.

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