Green propolis increases myeloid suppressor cells and CD4+Foxp3+ cells and reduces Th2 inflammation in the lungs after allergen exposure

J Ethnopharmacol. 2020 Apr 24:252:112496. doi: 10.1016/j.jep.2019.112496. Epub 2019 Dec 21.

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.

Keywords: Asthma; PMN-MDSC; Propolis; Treg cells.

MeSH terms

  • Allergens
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Differentiation / drug effects
  • Female
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Immunotherapy
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-5 / immunology
  • Lung / drug effects
  • Lung / immunology
  • Mice, Inbred C57BL
  • Myeloid-Derived Suppressor Cells / drug effects*
  • Myeloid-Derived Suppressor Cells / immunology
  • Ovalbumin
  • Propolis / pharmacology
  • Propolis / therapeutic use*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Allergens
  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Interleukin-13
  • Interleukin-5
  • Ovalbumin
  • Propolis