The Modulatory Effects of Vitamin D on the Expression of IL-12 and TGF-β in the Spinal Cord and Serum of Mice with Experimental Autoimmune Encephalomyelitis

Rayhaneh Ahangar-Parvin,Zuhair Muhammad Hassan ,Sayyed Vahab Azizi,Zahra Taghipour,Sayyed Mohammad Moazzeni,Maryam Nemati,Hossain Khorramdelazad ,Marzieyeh Mohammadi-Kordkhayli ,Abdollah Jafarzadeh

doi:10.30699/ijp.13.1.10

Abstract

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). 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. IL-12 gene expression and its serum levels in PBS-injected- or OO-administrated 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, OO-administrated 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). VD modulates the expression of IL-12 and TGF-β in spinal cord and serum of EAE mice.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune response-mediated inflammatory disease of the central nervous system (CNS), which results in neuronal demyelination and axonal degeneration [1]
IL-12 gene expression in EAE group treated with vitamin D (VD) was significantly decreased compared to PBS-injected- or olive oil (OO)-administrated EAE groups (P
Serum IL-12 levels were significantly reduced in VD-treated EAE mice compared to PBS-injected- or OO-administrated EAE groups (P

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune response-mediated inflammatory disease of the central nervous system (CNS), which results in neuronal demyelination and axonal degeneration [1]. The experimental model of MS disease is named autoimmune encephalomyelitis (EAE), which is inducible in susceptible animals by immunization with myelin-derived components. Rupture of the blood-brain barrier (BBB) and migration of activated leukocytes are among the earliest defects that occur in MS and EAE diseases [3]. Dendritic cells (DCs) migrate across the BBB and induce differentiation of naïve myelin specific naïve CD4+ T cells into pathogenic Th1 and Th17 that may be accountable for demyelination in MS and EAE [3, 4], while Treg cells may confer protection against diseases and the Th2 role remains controversial [4, 5]. Increased levels of a Th17 cell-related chemokine C-C motif ligand 20 (CCL20) and diminished levels of a Th2/Treg cellrelated chemokine C-C motif ligand 22 (CCL22) were observed in patients with MS [6, 7]

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