CGS 21680, an Agonist of the Adenosine (A2A) receptor, reduces progression of murine type II collagen-induced arthritis

Emanuela Mazzon, Emanuela Esposito, Daniela Impellizzeri, Rosanna Di Paola, Alessia Melani, Placido Bramanti, Felicita Pedata, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

Objective. The aim of our study was to investigate the effect of an adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-50 ethylcarboxamidoadenosine (CGS 21680), on modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). Methods. CIA was induced by intradermal injection of 100 μl of emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On Day 21, a second injection of CII in CFA was administered. Immunized mice developed erosive hind paw arthritis. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by Day 27 in the CII challenged mice and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of cartilage at the joint margins. Results. Treatment of mice with CGS 21680 starting at the onset of arthritis (Day 25) ameliorated the clinical signs at Days 26-35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in CGS 21680-treated mice as indicated by elevated levels of malondialdehyde, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of proinflammatory cytokines such as tumor necrosis factor, interleukin 1ß(IL-1ß) and IL-6 were also reduced by CGS 21680. Treatment with CGS 21680 also decreased the expression of inducible nitric oxide synthase and cyclooxygenase-2. Conclusion. We demonstrate that CGS 21680 exerts an antiinflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)2119-2129
Number of pages11
JournalJournal of Rheumatology
Volume38
Issue number10
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Adenosine
  • Apoptosis
  • Arthritis
  • CGS 21680
  • Inflammation

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

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