The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis
| Autor: | A. Boitelle, Lamyaa Al-Riyami, Katrina M. Houston, Caitlin Egan, T. Thalhamer, Dorothy E. Kean, William Harnett, Iain B. McInnes, Christina N. Steiger, Marcos J. C. Alcocer, JA Gracie, S. McGuiness, Margaret M. Harnett |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Inflammatory arthritis medicine.medical_treatment Phosphorylcholine Immunology Arthritis General Biochemistry Genetics and Molecular Biology Arthritis Rheumatoid Tissue Culture Techniques Mice Rheumatology Internal medicine medicine Immunology and Allergy Animals Humans Immunologic Factors Cells Cultured Autoimmune disease biology business.industry Anti-Inflammatory Agents Non-Steroidal Synovial Membrane Helminth Proteins medicine.disease Arthritis Experimental Recombinant Proteins Ovalbumin Cytokine Mice Inbred DBA Rheumatoid arthritis Immunoglobulin G biology.protein Cytokines Inflammation Mediators business |
| Zdroj: | Annals of the rheumatic diseases. 67(4) |
| ISSN: | 1468-2060 |
| Popis: | Objective:In countries where parasitic infections are endemic, autoimmune disease is relatively rare, leading to the hypothesis that parasite-derived immunomodulators may protect against its development. Consistent with this, we have previously demonstrated that ES-62, a 62 kDa phosphorylcholine (PC)-containing glycoprotein that is secreted by filarial nematodes, can exert anti-inflammatory action in the murine collagen-induced arthritis (CIA) model and human rheumatoid arthritis-derived synovial tissue cultures. As a first step to developing ES-62-based drugs, the aim of this study was to determine whether the PC-moiety of ES-62 was responsible for its anti-inflammatory actions.Methods:We compared the anti-inflammatory activity of a PC-free form of recombinant ES-62 (rES-62) and a synthetic PC-ovalbumin conjugate (OVA-PC) with that of native ES-62 in the CIA model and synovial tissues from patients with rheumatoid arthritis.Results:The anti-inflammatory actions of ES-62 in CIA appear to be dependent on the PC moiety as indicated by the reduction in severity of disease and also suppression of collagen-specific T helper 1 cytokine production observed when testing OVA-PC, but not rES-62. Interestingly, the anti-inflammatory activity of PC did not correlate with a reduction in anti-collagen IgG2a levels. Also, the ES-62-mediated suppression of interferon-γ from human patient tissues could be mimicked by OVA-PC but not rES-62 or ovalbumin.Conclusions:In countries where filariasis is endemic the reduced detection of inflammatory diseases, such as rheumatoid arthritis may be because of the anti-inflammatory action of the PC moieties of ES-62. PC may thus provide the starting point for the development of novel, safe immunomodulatory therapies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|