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

Arnold Postlethwaite, Maureen A. Holness, Hitoshi Katai, Rajendra Raghow

Research output: Contribution to journalArticle

390 Citations (Scopus)

Abstract

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 β-actin mRNA. Quantitative analysis of the levels of Pro α1(I) collagen transcripts in IL-4-treated flbroblast 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 α1(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.

Original languageEnglish (US)
Pages (from-to)1479-1485
Number of pages7
JournalJournal of Clinical Investigation
Volume90
Issue number4
DOIs
StatePublished - Jan 1 1992

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Extracellular Matrix Proteins
Interleukin-4
Fibroblasts
Collagen
Fibronectins
Messenger RNA
Collagen Type III
Mast Cells
Cytokines
T-Lymphocytes
Antisense RNA
Collagen Type I
Osteoarthritis
Wound Healing
Actins
Rheumatoid Arthritis
Fibrosis
Rabbits
Cell Line
Skin

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4. / Postlethwaite, Arnold; Holness, Maureen A.; Katai, Hitoshi; Raghow, Rajendra.

In: Journal of Clinical Investigation, Vol. 90, No. 4, 01.01.1992, p. 1479-1485.

Research output: Contribution to journalArticle

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