The ameliorative effects of capsidiol isolated from elicited Capsicum annuum on mouse splenocyte immune responses and neuroinflammation

초록

Capsidiol, is an anti-fungal phytoalexin produced by plants of Solanaceae. Capsidiol was examined in cultures of primary splenocytes (SPLCs) isolated from healthy C57BL/6 mice and from those with induced experimental autoimmune encephalomyelitis (EAE) as a mouse model for autoimmune neurodegenerative multiple sclerosis (MS). We also examined the impact of capsidiol in IFN-gamma-stimulated mouse BV2 microglial cells. Capsidiol resulted in a significant reduction in the anti-CD3/CD28 (alpha CD3/CD28)-induced IFN-gamma(+)CD4(+) (Th1) and IFN-gamma(+)CD8(+) (Tc1) populations as well as in the production of cytokines (IFN-gamma, IL-17A, IL-6, IL-2, TNF-alpha, and IP-10). Specifically, the CD4(+) and CD8(+) populations (T-bet(+)IFN-gamma(-), T-bet(+)IFN-gamma(+), and T-bet(-)IFN-gamma(+)) and cytokine production mediated by Th1/Tc1 polarization were diminished by 25 mu M capsidiol. MOG(35-55) restimulation of SPLCs from EAE mice resulted in an increase in antigen-specific T cells, including Th1, IL-17A(+)CD4(+) (Th17), and IL-17A(+)CD8(+) (Tc17) populations. By contrast, capsidiol resulted in a decrease in the proportions of Th17 and Tc17 cells; MOG(35-55)-specific cytokine production was also diminished by capsidiol. Capsidiol treatment resulted in diminished levels of IFN-gamma-induced nitric oxide and IL-6; expression of iNOS and COX-2 were suppressed by 50 mu M capsidiol in IFN-gamma-stimulated BV2 cells. This is the first report of capsidiol-mediated immunomodulatory and antineuroinflammatory activities that may serve to prevent neurodegeneration.

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