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Cited by 517

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Interleukin-1β and Tumor Necrosis Factor-α Decrease Collagen Synthesis and Increase Matrix Metalloproteinase Activity in Cardiac Fibroblasts In Vitro

Siwik, Deborah A., Chang, Donny L.-F., Colucci, Wilson S.·2000·Circulation Research

Abstract

Abstract —We tested the hypothesis that the inflammatory cytokines can regulate fibroblast extracellular matrix metabolism. Neonatal and adult rat cardiac fibroblasts cultures in vitro were exposed to interleukin (IL)–1β (4 ng/mL), tumor necrosis factor-α (TNF-α; 100 ng/mL), IL-6 (10 ng/mL), or interferon-γ (IFN-γ; 500 U/mL) for 24 hours. IL-1β, and to a lesser extent TNF-α, decreased collagen synthesis, which was measured as collagenase-sensitive [ 3 H]proline incorporation, but had no effect on cell number or total protein synthesis. IL-1β decreased the expression of procollagen α 1 (I), α 2 (I), and α1(III) mRNA, but increased the expression of procollagen α 1 (IV), α 2 (IV), and fibronectin mRNA, indicating a selective transcriptional downregulation of fibrillar collagen synthesis. IL-1β and TNF-α each increased total matrix metalloproteinase (MMP) activity as measured by in-gel zymography, causing specific increases in the bands corresponding to MMP-13, MMP-2, and MMP-9. IL-1β increased the expression of proMMP-2 and proMMP-3 mRNA, suggesting that increased metalloproteinase activity is due, at least in part, to increased transcription. The effects of IL-1β were not dependent on NO production. Thus, IL-1β and TNF-α decrease collagen synthesis and activate MMPs that degrade collagen. These observations suggest that IL-1β and TNF-α may contribute to ventricular dilation and myocardial failure by promoting the remodeling of interstitial collagen.

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Metadata

Authors
Siwik, D. A., Chang, D. L.-F., & Colucci, W. S.
Venue
Circulation Research
Published
2000-06-23
Volume
86
Issue
12
Pages
1259-1265
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2137421304
Cited by
517
References
48
FWCI
16.22
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Interleukin-1β and Tumor Necrosis Factor-α Decrease Collagen Synthesis and Increase Matrix Metalloproteinase Activity in Cardiac Fibroblasts In Vitro. https://app.cochat.ai/papers/10.1161/01.res.86.12.1259
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Siwik, D. A., Chang, D. L.-F., & Colucci, W. S. (2000). Interleukin-1β and Tumor Necrosis Factor-α Decrease Collagen Synthesis and Increase Matrix Metalloproteinase Activity in Cardiac Fibroblasts In Vitro. Circulation Research. https://doi.org/10.1161/01.res.86.12.1259

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