title: Participation of MCP-induced protein 1 in lipopolysaccharide preconditioning-induced ischemic stroke tolerance by regulating the expression of proinflammatory cytokines.
abstract: 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.
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, 4000 Central Florida Blvd, Orlando, FL 32816, USA. jian.liang@ucf.edu
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yasser
authors.initials: Y
authors.lastname: Saad
authors.forename: Logan
authors.initials: L
authors.lastname: Warble
authors.forename: Edilu
authors.initials: E
authors.lastname: Becerra
authors.forename: Pappachan E
authors.initials: PE
authors.lastname: Kolattukudy
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D019194:Ischemic Preconditioning; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012260:Ribonucleases / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D020521:Stroke / Q000276:immunology* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse