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.
Tanaka M, Okamoto Y, Fukui T, Masuzawa T
Inflammopharmacology Feb 2012
IL-17 is implicated in osteoporosis.
Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis.
Th17 cells produce IL-17, and the latter promotes bone loss in collagen-induced arthritis in mice. Blocking IL-17 action in mouse model of rheumatoid arthritis reduces disease symptoms. These observations suggest that Th17 cells may be involved in the pathogenesis of bone loss. However, the role of Th17 cell in estrogen (E2) deficiency-induced bone loss is still not very clear. We investigated the effect of E2 on Th17 differentiation in vivo and IL-17 mediated regulation of osteoclast and osteoblast differentiation. Additionally, effect of IL-17 functional block under E2 deficiency-induced bone loss was studied. In murine bone marrow cells, E2 suppressed IL-17 mediated osteoclast differentiation. IL-17 inhibited formation of mineralized nodules in osteoblasts and this effect was suppressed by E2. E2 treatment to mouse calvarial osteoblasts inhibited the IL-17-induced production of osteoclastogenic cytokines and NF-kB translocation. In ovariectomized mice, there was increase in the number of Th17 cells, transcription factors promoting Th17 cell differentiation and circulating IL-17 levels. These effects were reversed by E2 supplementation. Treatment of neutralizing IL-17 monoclonal antibody to Ovx mice mitigated the E2 deficiency-induced trabecular bone loss and reversed the decreased osteoprotegerin-to-receptor activator of nuclear factor kappa B ligand (RANKL) transcript levels in long bones, increased osteoclast differentiation from the bone marrow precursor cells and decreased osteoblast differentiation from the bone marrow stromal cells. Our findings indicate that E2 deficiency leads to increased differentiation of Th17 cells with attendant up regulation of STAT3, ROR-γt and ROR-α and downregulation of Foxp3 which antagonizes Th17 cell differentiation. Increased IL-17 production in turn induces bone loss by increasing pro-osteoclastogenic cytokines including TNF-α, IL-6 and RANKL from osteoblasts and functional block of IL-17 prevents bone loss. IL-17 thus plays a critical causal role in Ovx-induced bone loss and may be considered a potential therapeutic target in pathogenesis of post menopausal osteoporosis.
Tyagi AM, Srivastava K, Mansoori MN, Trivedi R…
PLoS ONE 2012
PMID: 22970248 | Free Full Text