Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4

J Clin Invest. 1992 Oct;90(4):1479-85. doi: 10.1172/JCI116015.


Interleukin 4 (also known as "B cell stimulatory factor-1"), a cytokine product of T lymphocytes and mast cells, stimulates synthesis of the extracellular matrix proteins, types I and III collagen and fibronectin, by human dermal fibroblasts in vitro. Stimulation of collagen by human recombinant (hr)IL-4 was also demonstrated in several fibroblastic synovial cell lines obtained from patients with rheumatoid arthritis and osteoarthritis. The stimulatory effect of hrIL-4 on fibroblast collagen synthesis was specifically neutralized by rabbit anti-hrIL-4 Ig. IL-4 specifically increased the steady-state levels of types I and III procollagen and fibronectin mRNAs, with no effect on cytoplasmic beta-actin mRNA. Quantitative analysis of the levels of Pro alpha 1(I) collagen transcripts in IL-4-treated fibroblast cultures was also corroborated by antisense RNA-mRNA hybridization and RNAse resistant hybrids which showed that IL-4-treated fibroblasts expressed higher levels of Pro alpha 1(I) collagen transcripts. Nuclear run-off transcription experiments indicated that IL-4 stimulated the rates of mRNA biogenesis. Based on these observations we conclude that IL-4 exerts its effect on collagen and fibronectin synthesis at the pretranslational level, resulting in synthesis of these extracellular matrix proteins. These and other data suggest that IL-4 may be a "fibrogenic cytokine" that could be important in promoting biogenesis of extracellular matrix proteins in normal wound healing and in pathological fibrosis in which mast cells and T lymphocytes play a central role.

Publication types

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

MeSH terms

  • Cells, Cultured
  • Collagen / biosynthesis*
  • Fibroblasts / metabolism
  • Fibronectins / biosynthesis*
  • Fibronectins / genetics
  • Humans
  • Interleukin-4 / pharmacology*
  • Procollagen / genetics
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology


  • Fibronectins
  • Procollagen
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-4
  • Collagen