Myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis is ameliorated in interleukin-32 alpha transgenic mice.

Jaesuk Yun,Mi Hee Park,Moon Soon Lee,Jin Tae Hong,Hyung Mun Yun,Sun Mi Gu,Dong Ju Son

doi:10.18632/oncotarget.6306

Abstract

Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disease in which myelin in the spinal cord and brain are damaged. IL-32α is known as a critical molecule in the pathophysiology of immune-mediated chronic inflammatory disease such as rheumatoid arthritis, chronic pulmonary disease, and cancers. However, the role of IL-32α on spinal cord injuries and demyelination is poorly understood. Recently, we reported that the release of proinflammatory cytokines were reduced in IL-32α-overexpressing transgenic mice. In this study, we investigated whether IL-32α plays a role on MS using experimental autoimmune encephalomyelitis (EAE), an experimental mouse model of MS, in human IL-32α Tg mice. The Tg mice were immunized with MOG35-55 suspended in CFA emulsion followed by pertussis toxin, and then EAE paralysis of mice was scored. We observed that the paralytic severity and neuropathology of EAE in IL-32α Tg mice were significantly decreased compared with that of non-Tg mice. The immune cells infiltration, astrocytes/microglials activation, and pro-inflammatory cytokines (IL-1β and IL-6) levels in spinal cord were suppressed in IL-32α Tg mice. Furthermore, NG2 and O4 were decreased in IL-32α Tg mice, indicating that spinal cord damaging was suppressed. In addition, in vitro assay also revealed that IL-32α has a preventive role against Con A stimulation which is evidenced by decrease in T cell proliferation and inflammatory cytokine levels in IL-32α overexpressed Jurkat cell. Taken together, our findings suggested that IL-32α may play a protective role in EAE by suppressing neuroinflammation in spinal cord.

Highlights

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system [1]
We demonstrated that cytokines were down regulated in IL-32α mice in comparison with those of non-Tg mice induced by EAE
The reduction of myelin basic protein (MBP) and CNPase was not rescued in IL-32α mice, the demyelination was attenuated in IL-32α mice

Summary

Introduction

MS is the most common inflammatory demyelinating disease of the central nervous system [1]. MS can lead to substantial disability with deficits seen in sensory, motor, autonomic, and neurocognitive function [2]. Its pathology is characterized by leukocyte infiltration, www.impactjournals.com/oncotarget demyelination, oligodendrocyte loss, axonal transection, and a reactive astrogliosis [4, 5]. It is believed that early neurologic disability in MS is affected by conduction block in demyelinated axons, whereas axonal transection underlies the more permanent deficits observed later in the disease [6]. For study of MS, the most common animal model of experimental autoimmune encephalomyelitis (EAE) induction is currently based on the injection of an encephalitogenic peptide, MOG35-55 as well as proteolipid protein and myelin basic protein. The MOG35-55 peptide triggers chronic-progressive EAE in C57BL mice

Methods

Results

Conclusion