» Articles » PMID: 10864917

Interleukin-1beta and Tumor Necrosis Factor-alpha Decrease Collagen Synthesis and Increase Matrix Metalloproteinase Activity in Cardiac Fibroblasts in Vitro

Overview
Journal Circ Res
Date 2000 Jun 24
PMID 10864917
Citations 170
Authors
Affiliations
Soon will be listed here.
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)-1beta (4 ng/mL), tumor necrosis factor-alpha (TNF-alpha; 100 ng/mL), IL-6 (10 ng/mL), or interferon-gamma (IFN-gamma; 500 U/mL) for 24 hours. IL-1beta, and to a lesser extent TNF-alpha, 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-1beta decreased the expression of procollagen alpha(1)(I), alpha(2)(I), and alpha1(III) mRNA, but increased the expression of procollagen alpha(1)(IV), alpha(2)(IV), and fibronectin mRNA, indicating a selective transcriptional downregulation of fibrillar collagen synthesis. IL-1beta and TNF-alpha 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-1beta 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-1beta were not dependent on NO production. Thus, IL-1beta and TNF-alpha decrease collagen synthesis and activate MMPs that degrade collagen. These observations suggest that IL-1beta and TNF-alpha may contribute to ventricular dilation and myocardial failure by promoting the remodeling of interstitial collagen.

Citing Articles

Anti-Inflammatory and Antioxidant Effects of White Grape Pomace Polyphenols on Isoproterenol-Induced Myocardial Infarction.

Pop R, Boarescu P, Bocsan C, Gherman M, Chedea V, Jianu E Int J Mol Sci. 2025; 26(5).

PMID: 40076654 PMC: 11900020. DOI: 10.3390/ijms26052035.


Emerging Role of Macrophage-Fibroblast Interactions in Cardiac Homeostasis and Remodeling.

Zhang X, Li Q, Tang T, Cheng X JACC Basic Transl Sci. 2025; 10(1):113-127.

PMID: 39958468 PMC: 11830265. DOI: 10.1016/j.jacbts.2024.06.003.


Relationship of Inflammatory Mediators (Interleukin and Cortisol Concentrations) with Corneal Epithelial Quantifiable Metrics.

Santhiago M, Stival L, Araujo D, Antunes-Foschini R, Toledo M, Nunes I Ophthalmol Sci. 2024; 5(1):100624.

PMID: 39624797 PMC: 11609233. DOI: 10.1016/j.xops.2024.100624.


Deciphering Collagen Phenotype Dynamics Regulators: Insights from In-Silico Analysis.

Rajalekshmi R, Rai V, Agrawal D J Bioinform Syst Biol. 2024; 7(3):169-181.

PMID: 39484658 PMC: 11526781. DOI: 10.26502/jbsb.5107089.


Uncovering the Therapeutic Potential of Lithium Chloride in Type 2 Diabetic Cardiomyopathy: Targeting Tau Hyperphosphorylation and TGF-β Signaling via GSK-3β Inhibition.

Abou Assi L, Alkhansa S, Njeim R, Ismail J, Madi M, Ghadieh H Pharmaceutics. 2024; 16(7).

PMID: 39065652 PMC: 11279906. DOI: 10.3390/pharmaceutics16070955.