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Anti-type II collagen antibody and interleukin 6 in the plasma and peptidases of plasma, synovia, synovium and circulating leukocytes from rats treated with collagen type II and Apis mellifera venom

Grant number: 07/08311-4
Support Opportunities:Regular Research Grants
Duration: July 01, 2008 - December 31, 2010
Field of knowledge:Biological Sciences - Physiology - Compared Physiology
Principal Investigator:Paulo Flávio Silveira
Grantee:Paulo Flávio Silveira
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


The administration of type-II collagen in rats produces an experimental model of auto-immunity, which is well-recognized to mimic rheumatoid arthritis. Rheumatoid arthritis affects about 1% of the worldwide population. It is characterised by cellular infiltration in the synovium, progressive erosion of cartilage and bone and pannus formation in the affected joints, as well the immune response to cartilage components and the presence of rheumatoid factors. Several mechanisms are involved in the disease establishment and chronicicity, as the activation of macrophages, neutrophils, linfocytes T and B and dendritic cells, formation of immune complexes, angiogenesis and release of cytokines and chemokines. Bee venom therapy has been used in oriental medicine to treat inflammatory diseases, as rheumatoid arthritis, by its property to decrease pain and inflammation. Moreover, the destruction of cartilage, inflammatory mechanisms and antigenic processing are related to aminopeptidases, such as neutral (APN), basic (APB) and dipeptidyl-peptidase IV, and to prolyl oligopeptidase (POP). The aims of the present project are to analyse: (1) the involvement of APN, APB, DPP-IV and POP activities in the plasma, synovia and synovium, as well in mononuclear and polymorphonuclear cells, ex vivo and in vitro, in rats administered with type-II collagen; and (2) if changes on the levels of these peptidase activities and inflammatory markers, such as anti-type II collagen antibody and interleukin (IL)-6, could be mitigated after treatment with Apis mellifera venom (BV) and/or methotrexate (MTX) (commonly used drug for rheumatoid arthritis). This project intends to bring light to the study of the etiology of rheumatoid arthritis and to evaluate the effects of BV and peptidase activities as diagnostic markers and therapeutic targets of this pathology. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
YAMASAKI, SIMONE CRISTINA; MURARI-DO-NASCIMENTO, STEPHANIE; SILVEIRA, PAULO FLAVIO. Neutral aminopeptidase and dipeptidyl peptidase IV in the development of collagen II-induced arthritis. Regulatory Peptides, v. 173, n. 1-3, p. 47-54, . (07/08311-4)
YAMASAKI, SIMONE C.; MENDES, MARIANA T.; ALPONTI, RAFAELA F.; SILVEIRA, PAULO F.. Efficacy of parenteral administration of bee venom in experimental arthritis in the rat: A comparison with methotrexate. Toxicon, v. 98, p. 75-88, . (07/08311-4)

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