Annie R Piñeros1, Mikhael H F de Lima2, Tamara Rodrigues3, Ana Flávia Gembre4, Thais B Bertolini5, Miriam D Fonseca6, Andresa A Berretta7, Leandra N Z Ramalho8, Fernando Q Cunha9, Juliana I Hori10, Vânia L D Bonato11. 1. Basic and Applied Immunology Program, Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: anniep93@gmail.com. 2. Basic and Applied Immunology Program, Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: mikhaelharuo@usp.br. 3. Basic and Applied Immunology Program, Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: tamararodrigues@usp.br. 4. Basic and Applied Immunology Program, Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: flagembre@yahoo.com.br. 5. Basic and Applied Immunology Program, Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: thabertolini@gmail.com. 6. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: miriamfarmacia@yahoo.com.br. 7. Apis Flora Industrial e Comercial Ltda, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: andresa.berretta@apisflora.com.br. 8. Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: lramalho@fmrp.usp.br. 9. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: fdqcunha@fmrp.usp.br. 10. Apis Flora Industrial e Comercial Ltda, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: juliana.hori@apisflora.com.br. 11. Basic and Applied Immunology Program, Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: vlbonato@fmrp.usp.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a natural product produced by honeybees used as a medicine at least to 300 BC. In the last decades, several studies showed biological and pharmacological properties of propolis, witch scientifically explains the empirical use for centuries. The anti-inflammatory activity of propolis with the purpose to reduce Th2 inflammation has been evaluated in allergic asthma. However, it remains to be determined how propolis negatively regulates the immune response after allergen re-exposure. AIM OF THE STUDY: We hypothesized that the anti-inflammatory activity of propolis is dependent on the induction of myeloid derived suppressor cells (MDSC) and regulatory T cells. MATERIALS AND METHODS: To assess this hypothesis, we used an ovalbumin-induced asthma model to evaluate the effect of EPP-AF® dry extract from Brazilian green propolis. RESULTS: Propolis treatment decreased pulmonary inflammation and mucus production as well as eosinophils and IL-5 in the broncoalveolar lavage. Propolis enhanced also in vitro differentiation and in vivo frequency of lung MDSC and CD4+Foxp3+ regulatory T cells. CONCLUSIONS: Together these results confirm the immunomodulatory potential of propolis during sensitization and challenge with allergen. In addition, the collecting findings show, for the first time, that propolis increases the frequency of MDSC and CD4+Foxp3+ regulatory T cells in the lungs, and suggest that it could be use as target for development of new immunotherapy or adjuvant immunotherapy for asthma.
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a natural product produced by honeybees used as a medicine at least to 300 BC. In the last decades, several studies showed biological and pharmacological properties of propolis, witch scientifically explains the empirical use for centuries. The anti-inflammatory activity of propolis with the purpose to reduce Th2 inflammation has been evaluated in allergic asthma. However, it remains to be determined how propolis negatively regulates the immune response after allergen re-exposure. AIM OF THE STUDY: We hypothesized that the anti-inflammatory activity of propolis is dependent on the induction of myeloid derived suppressor cells (MDSC) and regulatory T cells. MATERIALS AND METHODS: To assess this hypothesis, we used an ovalbumin-induced asthma model to evaluate the effect of EPP-AF® dry extract from Brazilian green propolis. RESULTS: Propolis treatment decreased pulmonary inflammation and mucus production as well as eosinophils and IL-5 in the broncoalveolar lavage. Propolis enhanced also in vitro differentiation and in vivo frequency of lung MDSC and CD4+Foxp3+ regulatory T cells. CONCLUSIONS: Together these results confirm the immunomodulatory potential of propolis during sensitization and challenge with allergen. In addition, the collecting findings show, for the first time, that propolis increases the frequency of MDSC and CD4+Foxp3+ regulatory T cells in the lungs, and suggest that it could be use as target for development of new immunotherapy or adjuvant immunotherapy for asthma.
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