Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein beta knockout mice following transient focal cerebral ischemia.
CCAAT/enhancer binding protein beta (C/EBPbeta) is a leucine-zipper transcription factor that regulates cell growth and differentiation in mammals. Expression of many pro-inflammatory genes including the cytokine interleukin-6 is known to be controlled by C/EBPbeta. We report that focal cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO) significantly increases C/EBPbeta gene expression in mouse brain at between 6 and 72 h of reperfusion. To understand the functional significance of C/EBPbeta in postischemic inflammation and brain damage, we induced transient MCAO in cohorts of adult C/EBPbeta null mice and their wild-type littermates. At 3 days of reperfusion following transient MCAO, C/EBPbeta null mice showed significantly smaller infarcts, reduced neurological deficits, decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, decreased intercellular adhesion molecule 1 (ICAM1) immunopositive vessels, decreased extravasated neutrophils and fewer activated microglia/macrophages, compared with their wild-type littermates. Furthermore, GeneChip analysis showed that postischemic induction of many transcripts known to promote inflammation and neuronal damage was less pronounced in the brains of C/EBPbeta-/- mice compared with C/EBPbeta+/+ mice. These results suggest a significant role for C/EBPbeta in postischemic inflammation and brain damage.
Kapadia
Ramya
R
Department of Neurological Surgery, Universit of Wisconsin, Madison, Wisconsin, USA.
Tureyen
Kudret
K
Bowen
Kellie K
KK
Kalluri
Haviryaji
H
Johnson
Peter F
PF
Vemuganti
Raghu
R
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency* / Q000235:genetics; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology; D004660:Encephalitis / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D009474:Neurons / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D022782:CCAAT-Enhancer-Binding Protein-beta; D015850:Interleukin-6; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1