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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway

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Autor(es):
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Fonseca, D. M. [1] ; Wowk, P. F. [1] ; Paula, M. O. [1] ; Campos, L. W. [1] ; Gembre, A. F. [1] ; Turato, W. M. [1] ; Ramos, S. G. [2] ; Dias-Baruffi, M. [3] ; Barboza, R. [4] ; Gomes, E. [4] ; Silva, C. L. [1] ; Russo, M. [4] ; Bonato, V. L. D. [1]
Número total de Autores: 13
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pathol, Ribeirao Preto - Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol Bromatol Anal, Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Ribeirao Preto - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: CLINICAL AND EXPERIMENTAL ALLERGY; v. 42, n. 1, p. 131-143, JAN 2012.
Citações Web of Science: 12
Resumo

Background Previous studies have established that mycobacterial infections ameliorate allergic inflammation. However, a non-infectious approach that controls allergic responses might represent a safer and more promising strategy. The 60-65 kDa heat shock protein (Hsp) family is endowed with anti-inflammatory properties, but it is still unclear whether and how single mycobacterial Hsp control allergic disorders. Objective Therefore, in this study we determined whether the administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid could attenuate a previously established allergic response. Methods We used an experimental model of airway allergic inflammation to test the effects of immunotherapy with DNA encoding Hsp65. Allergic mice, previously sensitized and challenged with ovalbumin, were treated with tree intramuscular doses of recombinant DNA encoding Hsp65. After treatment, mice received a second allergen challenge and the allergic response was measured. Results We found that immunotherapy attenuated eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production. Moreover, we showed that the inhibition of allergic response is dependent on IL-10 production. Both Hsp65 and allergen-specific IL-10-producing cells contributed to this effect. Cells transferred from DNA-immunized mice to allergic mice migrated to allergic sites and down-modulated the Th2 response. Conclusions and Clinical Relevance Our findings clearly show that immunotherapy with DNA encoding Hsp65 can attenuate an established Th2 allergic inflammation through an IL-10-dependent mechanism; moreover, the migration of allergen-and Hsp65-specific cells to the allergic sites exerts a fundamental role. This work represents a novel contribution to the understanding of immune regulation by Hsp65 in allergic diseases. (AU)

Processo FAPESP: 05/59198-8 - Avaliacao do efeito imunomodulador da vacina dna-hsp65 na alergia experimental.
Beneficiário:Denise Morais da Fonseca
Modalidade de apoio: Bolsas no Brasil - Doutorado