CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis

Journal of Neuroinflammation

Luc Vallières¹  Aline Dumas¹  Jean-François Richard¹  Monica Roy¹ 

[1] Department of Endocrinology and Genomics, Laval University Hospital Research Center, 2705 Laurier Boulevard, Quebec G1V 4G2, QC, Canada

关键词: Autoimmunity.;    Cerebral endothelium;    Neutrophils;    Polymorphonuclear cells;    Myeloid cells;    Chemotaxis;    Neuroimmunity;    Neuroinflammation;   

Others  :  1212848
DOI  :  10.1186/1742-2094-9-18

 received in 2011-11-15, accepted in 2012-01-23,  发布年份 2012

【 摘 要 】

Background

Granulocytes generally exert protective roles in the central nervous system (CNS), but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE), the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined.

Methods

CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and in situ hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques.

Results

CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS) or pertussis toxin (PTX), the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease.

Conclusions

This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.

【 授权许可】

   
2012 Roy et al; licensee BioMed Central Ltd.

【 图 表 】

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