Cited by 504Wound Healing and TreatmentsTGF-β signaling in diseasesCardiac Fibrosis and Remodeling

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

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Postlethwaite, A E, Holness, M A, Katai, H, Raghow, R·1992·Journal of Clinical Investigation

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 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.

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Authors
Postlethwaite, A. E., Holness, M. A., Katai, H., & Raghow, R.
Affiliations
  • University of Tennessee Health Science Center (US)
  • Veterans Health Administration (US)
Venue
Journal of Clinical Investigation
Published
1992-10-01
Volume
90
Issue
4
Pages
1479-1485
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2049706385
Cited by
504
References
30
Citations by year
2026: 9 · 2025: 5 · 2024: 8 · 2023: 12 · 2022: 9 · 2021: 13 · 2020: 8 · 2019: 10 · 2018: 8 · 2017: 14 · 2016: 13 · 2015: 15 · 2014: 9 · 2013: 12 · 2012: 11
FWCI
20.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Institutes of Health (5r01ar026034-13)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50AR039166, AR39166, AR 26034)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
IL-4, dermal fibroblasts, extracellular matrix proteins, collagen synthesis, type I collagen, type III collagen, fibronectin, procollagen mRNA, rheumatoid arthritis, osteoarthritis, synovial fibroblasts, fibrosis, wound healing, mast cells, T cells
MeSH terms
Cells, Cultured, Collagen, Fibroblasts, Fibronectins, Humans, Procollagen, Recombinant Proteins, RNA, Messenger, Interleukin-4

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