Evaluation of the influence of prostaglandin E2 on recombinant equine interleukin-1beta-stimulated matrix metalloproteinases 1, 3, and 13 and tissue inhibitor of matrix metalloproteinase 1 expression in equine chondrocyte cultures.
Abstract: To determine the effects of prostaglandin E2 (PGE2) on recombinant equine interleukin (IL)-1beta-stimulated expression of matrix metalloproteinases (MMP 1, MMP 3, MMP 13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP 1) in vitro. Methods: Cultured equine chondrocytes. Methods: Stationary monolayers of first-passage chondrocytes were exposed to graduated concentrations of PGE2 with or without a subsaturating dose (50 pg/ml) of recombinant equine IL-1beta (reIL-1beta) to induce expression of MMP 1, MMP 3, MMP 13, and TIMP 1, followed by RNA isolation and northern blotting. In subsequent experiments, gene expression was similarly quantified from mRNA isolated from cultures pretreated with phenylbutazone to quench endogenous PGE2 synthesis, followed by exposure to reIL-1beta and exogenous PGE2 (5 mg/ml) with appropriate controls. Results: Exogenous PGE2 (10 mg/ml) significantly reduced reIL-1beta-induced expression of MMP 1, MMP 3, MMP 13, and TIMP 1. Abrogation of cytokine induction with this dose of PGE2 was comparable to that for dexamethasone (10(-5) M) control. Similarly, pretreatment with phenylbutazone, followed by exposure to relL-1beta and PGE2 (5 mg/ml), was associated with a reduced expression of the genes of interest, an effect that was significant for MMP 1, MMP 13, and TIMP 1. Conclusions: The MMP and TIMP 1 are important mediators in the pathophysiologic events in osteoarthritis. The potential for physiologically relevant regulation of expression of these genes by PGE2 is a consideration in the use of drugs that inhibit prostanoid synthesis in the treatment of equine arthropathies.
Publication Date: 2002-07-18 PubMed ID: 12118680DOI: 10.2460/ajvr.2002.63.987Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This research article investigates the effect of prostaglandin E2 (PGE2) on the expression of certain matrix metalloproteinases, specifically MMP 1, MMP 3, MMP 13, and TIMP 1, in horse cartilage cells stimulated by interleukin-1beta. Findings suggest PGE2 can potentially influence the production of these proteins, which could impact the treatment of horse joint diseases.
Objective and Methodology
- The researchers aimed to determine how PGE2, a natural substance produced in the body that can cause inflammation and pain, influences the way cartilage cells produce various matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMP1) when stimulated by interleukin-1beta. MMPs are proteins that break down connective tissue, while TIMP1 is a protein that specifically inhibits MMP activity.
- Experiments involved growing horse-cartilage cells in a lab environment and exposing them to varying concentrations of PGE2, either alone or combined with interleukin-1beta.
- This experiment was repeated with cells treated with phenylbutazone to stop the production of endogenous PGE2, then the cells were exposed to external PGE2 and interleukin-1beta.
- Gene expressions were measured and compared among the different treatments.
Results and Findings
- The researchers discovered that the addition of external PGE2 reduced the production of MMP 1, MMP 3, MMP 13, and TIMP 1 in cells stimulated by interleukin-1beta. This impact was equivalent to the control group treated with dexamethasone, a corticosteroid that reduces inflammation.
- The inhibitory effect was also observed in the group treated with phenylbutazone and then exposed to PGE2 and interleukin-1beta.
Conclusions and Implications
- The research suggests that MMPs and TIMP1 play crucial roles in the development of osteoarthritis, a common joint disease in horses. How PGE2 controls the expression of these genes could be important in developing drugs for treating joint disorders in horses.
- The results also suggest potential implications for treatment protocols: Current treatments for arthropathies often involve the use of nonsteroidal anti-inflammatory drugs, such as phenylbutazone, to inhibit prostaglandin synthesis – however, this may indirectly influence the production of critical MMPs and TIMP1.
Cite This Article
APA
Tung JT, Arnold CE, Alexander LH, Yuzbasiyan-Gurkan V, Venta PJ, Richardson DW, Caron JP.
(2002).
Evaluation of the influence of prostaglandin E2 on recombinant equine interleukin-1beta-stimulated matrix metalloproteinases 1, 3, and 13 and tissue inhibitor of matrix metalloproteinase 1 expression in equine chondrocyte cultures.
Am J Vet Res, 63(7), 987-993.
https://doi.org/10.2460/ajvr.2002.63.987 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing 48824, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Blotting, Northern / veterinary
- Chondrocytes / cytology
- Chondrocytes / drug effects
- Chondrocytes / enzymology
- Dinoprostone / pharmacology
- Drug Interactions
- Gene Expression Regulation, Enzymologic / drug effects
- Horses / metabolism
- Interleukin-1 / pharmacology
- Matrix Metalloproteinases / biosynthesis
- Matrix Metalloproteinases / genetics
- Phenylbutazone / pharmacology
- RNA / chemistry
- RNA / genetics
- Recombinant Proteins / pharmacology
- Reverse Transcriptase Polymerase Chain Reaction / veterinary
- Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
- Tissue Inhibitor of Metalloproteinase-1 / genetics
Citations
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