Avaliação do efeito imunomodulatório de agonistas de PPAR-γ no recrutamento de eosinófilos

• Ano de defesa: 2011
• Autor(a) principal: FARNESI, Thaís Soares
• Orientador(a): NAPIMOGA, Marcelo Henrique
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Triângulo Mineiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Fisiológicas
• Departamento: Instituto de Ciências da Saúde - ICS::Curso de Medicina
• País: Brasil
• Palavras-chave em Português: PPAR-γ.; Eosinófilos.; Prostaglandina.; Inflamação.
• Palavras-chave em Inglês: PPAR-γ.; Eosinophils.; Prostaglandin.; Inflammation.
• Área do conhecimento CNPq: Ciências Biológicas
• Link de acesso: http://bdtd.uftm.edu.br/handle/tede/944

Eosinophils are essential cells in the allergic and parasitic inflammatory processes, as well as one of the main cells expressing the Peroxisome ProliferatorActivated Receptor-gamma (PPAR-γ). The PPAR-γ ligands negatively regulate the cells of the innate and adptative immune system and present excellent results in different models of inflammatory diseases, suggesting the use these ligands as therapeutic agents in different diseases. However, few studies have evaluated the effects of these ligands and the relationship with eosinophils and the allergic process. Thus, in this study we used the PPAR-γ ligands, 15d-PGJ2 and rosiglitazone (RGZ), in order to evaluate the effects in the eosinophilic recruitment and the regulation of eosinopoiesis in an eosinophilic model. C57Bl/6 wild type (C57Bl/6 WT) and C57Bl/6 knouckout for interleukin-17 (C57Bl/6 IL-17-/-), received a subcutaneous implant of heat-coagulated egg white (EWI), that induced an eosinophilic inflammation. After 15 days the mice were received a pretreatment with different doses of 15d-PGJ2 (100, 300 and 1000 µg/kg, of 12-12 hs, s.c.) and RGZ (1, 3 and 10mg/kg, of 24-24hs, v.o.), 30 minutes before allergenic challenge with ovalbumin (10ug/animal i.p.), and so evaluated the effects of these drugs on eosinophilic recruitment, 48 hours after challenge. The cytokines (IL-5, IL-33, IL-17 and IL-23) and IgE were measured by ELISA, from the peritoneal fluid and serum, respectively. According with results were possible determinate 15d-PGJ2 significantly reduced eosinophil recruitment to the peritoneal cavity (300 and 1000ug/kg), however only the dose of 1000ug/kg was able to down-regulate the bone marrow eosinopoiesis. The RGZ also showed similar effect, and the effective dose was 10mg/kg. The synthesis of IL-5 was decreased after treatment with 15d-PGJ2 (1000ug/Kg) and RGZ (10mg/Kg) corroborating with the eosinophilic recruitment, since IL-5 acts selectively on the eosinophilic lineage, promoting eosinopoiesis, recruitment, activation and survival of the eosinophils. Interesting, the serum IgE was decreased only after the administration of 1000ug/Kg of 15d-PGJ2. In this eosinophilia model, decreased synthesis of IL-33, IL-17 and IL- 23 was also observed. The IL-17-/- transgenic mice subjected to surgery failed to develop an allergic response, showing the importance of this cytokine to mount an allergic inflammatory response. Both PPAR-γ agonists are able to modulate the eosinophilic response, decreasing synthesis of Th2 specifics citokynes and citokynes of others profiles, as Th17, and the IgE modulation were observed only with the use of 15d-PGJ2 (1000ug/Kg). Thus, our results suggest that PPAR-γ agonists, mainly 15d-PGJ2, could be a good therapeutic strategy for eosinophil-mediated disorders.