Nitric oxide inhibits CXCL12 expression in neuroinflammation

被引:24
|
作者
Petkovic, Filip [1 ]
Blazevski, Jana [1 ]
Momcilovic, Miljana [1 ]
Stojkovic, Marija Mostarica [2 ]
Miljkovic, Djordje [1 ]
机构
[1] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Dept Immunol, Belgrade 11000, Serbia
[2] Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Belgrade 11000, Serbia
来源
IMMUNOLOGY AND CELL BIOLOGY | 2013年 / 91卷 / 06期
关键词
astrocyte; CXCL12; endothelial cell; experimental autoimmune encephalomyelitis; multiple sclerosis; nitric oxide; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NF-KAPPA-B; MULTIPLE-SCLEROSIS; UP-REGULATION; INDUCIBLE ISOFORM; SPINAL-CORD; IN-VITRO; T-CELLS;
D O I
10.1038/icb.2013.23
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chemokine CXCL12 (C-X-C motif chemokine ligand 12) restricts immune cell invasion of the central nervous system (CNS) and limits neuroinflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of inflammatory and demyelinating disease of the CNS, multiple sclerosis (MS). Nitric oxide (NO), by contrast, predominantly contributes to CNS tissue destruction in MS and EAE. Thus, the influence of NO on CXCL12 in the inflamed CNS was investigated. Excess expression of inducible NO synthase was inversely correlated to CXCL12 gene expression in spinal cord homogenates of rats immunized to develop EAE. NO inhibited gene expression of CXCL12 in astrocytes and endothelial cells in vitro. The inhibition was paralleled with reduction of p38 mitogen-activated protein kinase (MAPK) phosphorylation and it was mimicked with inhibitors of p38 MAPK activation in astrocytes. In vivo suppression of nitric generation recovered CXCL12 expression in the CNS and attenuated EAE in Dark Agouti rats. On the contrary, in vivo NO donation decreased CXCL12 expression in the CNS of EAE-resistant Albino Oxford (AO) rats. However, the effect was not paralleled with induction of EAE in AO rats. It is suggested that NO acting through suppression of p38 MAPK inhibits CXCL12 expression in neuroinflammation. These results imply that downregulation of NO release and protection of CXCL12 expression within the CNS might present the potential approaches in MS therapy.
引用
收藏
页码:427 / 434
页数:8
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