Reduction in the Evolution of Murine Type II Collagen-Induced Arthritis by Treatment with Rosiglitazone, a Ligand of the Peroxisome Proliferator-Activated Receptor γ

Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, N. S A Patel, Ivana Serraino, Rosanna Di Paola, Tiziana Genovese, Domenico Britti, Massimo De Maio, Achille P. Caputi, Christoph Thiemermann

Research output: Contribution to journalArticle

Abstract

Objective. The peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The thiazolidinedione rosiglitazone is a PPARγ ligand that modulates the transcription of target genes. The aim of this study was to investigate the effects of rosiglitazone on the inflammatory response in mice with collagen-induced arthritis (CIA). Methods. CIA was induced in DBA/1J mice by an intradermal injection of 100 μl of an emulsion of bovine type II collagen (CII; 100 μg) in Freund's complete adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Rosiglitazone (10 mg/kg/day) or vehicle (10% DMSO) was administered beginning on day 25 (arthritis onset) until day 35. Clinical, radiographic, histopathologic, and laboratory assessments were performed. Results. Mice immunized with CII in CFA developed erosive arthritis of the hind paws. Macroscopic evidence of CIA first appeared as periarticular erythema and edema of the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged mice, and the severity progressed over the 35-day study period. Radiographic evaluation revealed focal resorption of bone. Histopathologic features of CIA included erosion of cartilage at the joint margins. Rosiglitazone treatment ameliorated the clinical signs on days 26-35 and improved the histologic findings in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in rosiglitazone-treated mice, as indicated by elevation of malondialdehyde levels, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of the proinflammatory cytokines tumor necrosis factor, interleukin-1β, and interleukin-6 were also significantly reduced by rosiglitazone treatment. Conclusion. These data demonstrate that rosiglitazone exerts an antiinflammatory effect on chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

Original languageEnglish
Pages (from-to)3544-3556
Number of pages13
JournalArthritis and Rheumatism
Volume48
Issue number12
DOIs
Publication statusPublished - Dec 2003

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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    Cuzzocrea, S., Mazzon, E., Dugo, L., Patel, N. S. A., Serraino, I., Di Paola, R., Genovese, T., Britti, D., De Maio, M., Caputi, A. P., & Thiemermann, C. (2003). Reduction in the Evolution of Murine Type II Collagen-Induced Arthritis by Treatment with Rosiglitazone, a Ligand of the Peroxisome Proliferator-Activated Receptor γ. Arthritis and Rheumatism, 48(12), 3544-3556. https://doi.org/10.1002/art.11351