Participation of MCP-induced protein 1 in lipopolysaccharide preconditioning-induced ischemic stroke tolerance by regulating the expression of proinflammatory cytokines

Journal of Neuroinflammation

Pappachan E Kolattukudy¹  Edilu Becerra¹  Logan Warble¹  Yasser Saad¹  Jing Wang¹  Jian Liang¹ 

[1]Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, 4000 Central Florida Blvd. Orlando, FL 32816, USA

关键词: proinflammatory cytokines;    middle cerebral artery occlusion (MCAO);    monocyte chemotactic protein-induced protein 1 (MCPIP1);    lipopolysaccharide (LPS) preconditioning;    Ischemic stroke;   

Others  :  1212929
DOI  :  10.1186/1742-2094-8-182

 received in 2011-08-10, accepted in 2011-12-24,  发布年份 2011

【 摘 要 】

Background

Lipopolysaccharide (LPS) preconditioning-induced neuroprotection is known to be related to suppression of the inflammatory response in the ischemic area. This study seeks to determine if monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified CCCH Zn finger-containing protein, plays a role in focal brain ischemia and to elucidate the mechanisms of LPS-induced ischemic brain tolerance.

Methods

Transcription and expression of MCPIP1 gene was monitored by qRT-PCR and Western blot. Mouse microglia was prepared from cortices of C57BL/6 mouse brain and primary human microglia was acquired from Clonexpress, Inc. Wild type and MCPIP1 knockout mice were treated with LPS (0.2 mg/kg) 24 hours before brain ischemia induced by transient middle cerebral artery occlusion (MCAO). The infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining.

Results

MCPIP1 protein and mRNA levels significantly increased in both mouse and human microglia and mouse brain undergoing LPS preconditioning. MCPIP1 mRNA level significantly increased in mice ipsilateral brain than that of contralateral side after MCAO. The mortality of MCPIP1 knockout mice was significantly higher than that of wild-type after MCAO. MCPIP1 deficiency caused significant increase in the infarct volume compared with wild type mice undergoing LPS preconditioning. MCPIP1 deficiency caused significant upregulation of proinflammatory cytokines in mouse brain. Furthermore, MCPIP1 deficiency increased c-Jun N terminal kinase (JNK) activation substantially. Inhibition of JNK signaling decreased the production of proinflammatory cytokines in MCPIP1 knock out mice after MCAO.

Conclusions

Our data indicate that absence of MCPIP1 exacerbates ischemic brain damage by upregulation of proinflammatory cytokines and that MCPIP1 participates in LPS-induced ischemic stroke tolerance.

【 授权许可】

   
2011 Liang et al; licensee BioMed Central Ltd.

【 图 表 】

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