Suppression of interleukin 17 production by Brazilian propolis in mice with collagen-induced arthritis
Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. Propolis has been reported to have immunomodulatory activity. We hypothesized that propolis would be able to reduce the disease severity of rheumatoid arthritis. We evaluated the effect of Brazilian propolis ethanolic extract on the pathogenesis of collagen-induced arthritis (CIA) in mice. Mice fed propolis exhibited significant lower clinical arthritis scores than those fed the control diet. To investigate the mechanism of the effect of propolis on CIA mice, we examined interleukin-17 (IL-17) production in CIA mice fed propolis using an enzyme-linked immunospot assay and flow cytometric analysis. The numbers of IL-17-producing cells in the CIA mice fed propolis were significantly decreased. To determine direct influence of propolis on cytokine production, splenocytes were stimulated with phorbol myristate acetate in the presence of propolis extract in vitro. Concentration-dependent declines in IL-17 expression were observed by ELISA and real-time PCR methods. We further found that propolis significantly inhibited the differentiation of Th17 cells from murine splenocytes in a concentration-dependent manner. Taken together, our results may provide a new light on the potential mechanism of the immunosuppressive and anti-inflammatory effects of propolis.
KeywordsPropolis Interleukin-17 (IL-17) Collagen-induced arthritis (CIA)
The authors wish to thank Yamada Apiculture Center, Inc, Okayama Japan, for their generous provision of the propolis extracts. Part of this work was supported by a Grant provided by Yamada Bee Farm Grant for Honeybee Research.
- Cho ML, Kang JW, Moon YM, Nam HJ, Jhun JY, Heo SB, Jin HT, Min SY, Ju JH, Park KS, Cho YG, Yoon CH, Park SH, Sung YC, Kim HY (2006) STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J Immunol 176:5652–5661PubMedGoogle Scholar
- Korkina LG (2007) Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health. Cell Mol Biol (Noisy-le-grand) 53:15–25Google Scholar
- Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50:650–659PubMedCrossRefGoogle Scholar
- Orsatti CL, Missima F, Pagliarone AC, Bachiega TF, Bufalo MC, Araujo JP, Jr., Sforcin JM (2010) Propolis immunomodulatory action in vivo on Toll-like receptors 2 and 4 expression and on pro-inflammatory cytokines production in mice. Phytother Res 24:1141–1146Google Scholar
- Pappu BP, Dong C (2007) Measurement of interleukin-17. Curr Protoc Immunol Chapter 6: Unit 6 25Google Scholar
- Tani H, Hasumi K, Tatefuji T, Hashimoto K, Koshino H, Takahashi S (2010) Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes. Bioorg Med Chem 18:151–157Google Scholar