| Pharmacological purinergic P2X antagonism in the treatment of experimental collagen-induced arthritis. | |
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MedLine Citation:
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PMID: 21792831 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE.: The aim of the present study was to assess the therapeutic potential of a P2X purinergic receptor antagonist, namely periodate oxidized ATP (oATP), in collagen-induced arthritis (CIA). METHODS.: Arthritis was induced in male DBA/1J mice by immunization with type II collagen. Animals showing digits inflammation and paw swelling were treated intraperitoneally each day for 10 days with 100 μl of 3 mM oATP. At the end of treatment animals were sacrificed and paws removed for histological analysis and evaluation of T-cell infiltration. Humoral response to type II collagen was analyzed and specific serum autoantibody levels were correlated to the clinical score observed in the different animal groups. RESULTS: oATP treatment resulted in a sustained reduction of disease activity, which was associated with a significant decrease in CD3+ T-cells infiltration in arthritic lesions and a significant amelioration of cartilage erosion. Peripheral regulatory T cells (Tregs) were significantly increased upon P2X blockade in lymph nodes. Moreover, a marked reduction of circulating autoantibodies directed against mouse collagen type II wasdetected. CONCLUSIONS.: Our findings indicate that P2X receptor antagonism has an important therapeutic potential for chronic inflammatory rheumatic disorders. The therapeutic efficacy was associated with an increase of Tregs in secondary lymphoid organs. Notably, we observed a significant correlation between serum autoantibodies and clinical efficacy exerted by oATP treatment. Together these results underscore the potential value of the P2X receptor signaling pathway as a potential pharmacological target for the modulation of adaptive immunity in CIA. |
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Authors:
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Vittoria Ardissone; Enrico Radaelli; Paola Zaratin; Michele Ardizzone; Christoph Ladel; Marco Gattorno; Alberto Martini; Fabio Grassi; Elisabetta Traggiai |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-26 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 by the American College of Rheumatology. |
Affiliation:
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Department of in vivo Pharmacology, Merck Serono S.A. RBM S.p.A.- Istituto di Ricerche Biomediche "A. Marxer" Via Ribes, 1 Colleretto Giacosa (TO), Italy and Second Division of Pediatrics, IRCCS G. Gaslini, Largo G. Gaslini 5, Genoa, 16148, Italy. vittoria.ardissone@procelltech.net. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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