Chemokines facilitate the leukocytes infiltration into the central nervous system (CNS) which is an essential step in the pathogenesis of multiple sclerosis. Ginger has also a broad anti-inflammatory properties. The aim was to evaluate the effects of ginger extract on the expression of CCL20 and CCL22 and their receptors (CCR6 and CCR4, respectively) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice used for EAE induction by immunization with myelin oligodendroglial glycoprotein. Then, the EAE mice were treated with PBS or ginger extract, from day +3 to +30. At day 31, mice were scarified and the expression of CCL20 and CCL22 and their receptors in the spinal cord measured using real time-PCR. The expression of CCL20, CCL22 and CCR4 in the spinal cord of PBS-administrated EAE mice was significantly higher than healthy group (P<0.04, P<0.05 and P<0.02, respectively). In 200- and 300 mg/kg ginger extract-treated EAE mice, the expression of CCL20, CCL22 and CCR4 were significantly reduced as compared with PBS-administrated EAE group (P<0.04, P<0.01 and P<0.002 for 200 mg/kg ginger extract and P<0.01, P<0.005 and P<0.004 for 300 mg/kg ginger extract, respectively). The CCR6 expression in EAE mice treated with 200- or 300 mg/kg ginger extracts was lower than PBS-administrated EAE mice (P<0.01 and P=0.07, respectively). Treatment of EAE mice with ginger extract down-regulate the expression of CCL20 and CCL22 and their receptors in EAE mice. The possible therapeutic potential of ginger for treatment of MS can be considered in future investigations.
VD down-regulates the expression of some inflammatory cytokines, chemokines and chemokine receptors in EAE mice. The possible therapeutic potential of VD in multiple sclerosis can be considered in future investigation.
KEYWORDS ABSTRACTExperimental Autoimmune Encephalomyelitis Vitamin D IL-12 TGF-β
Background & objective:The immunoregulatory effects of transforming growth factor (TGF)-βand interleukin-12 (IL-12) and immunomodulatory actions of vitamin D (VD) were reported in several studies. This study aims to evaluate VD effects on IL-12 and TGF-β expression in experimental autoimmune encephalomyelitis (EAE).Methods: EAE was induced in three groups of C57BL/6 mice by immunization with MOG and administered intra-peritoneally 200 ngVD, PBS or olive oil (OO) from day +3 to +30. One group was also considered as healthy control group. At day 31, cytokines expression in the spinal cord and their serum levels were determined using real time-PCR and ELISA, respectively.Results: IL-12 gene expression and its serum levels in PBS-injected-or OOadministrated EAE groups were significantly higher than healthy group. IL-12 gene expression in EAE group treated with VD was significantly decreased compared to PBS-injected-or OO-administrated EAE groups (P<0.001 and P<0.02, respectively). Serum IL-12 levels were significantly reduced in VD-treated EAE mice compared to PBS-injected-or OO-administrated EAE groups (P<0.004 and P<0.05, respectively). No significant difference was observed between PBS-injected-EAE, OOadministrated EAE and healthy groups regarding the expression of TGF-β. In EAE mice treated with VD, TGF-β expression was significantly higher than healthy group and PBS-injected EAE mice (P<0.01 and P<0.04, respectively). VD-treated EAE group had also higher serum TGF-β levels than PBS-injected-, OO-administrated and healthy groups (P<0.05).Conclusion: VD modulates the expression of IL-12 and TGF-β in spinal cord and serum of EAE mice.
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