Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion.
CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappaB, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappaB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.
Kunz
Alexander
A
Division of Neurobiology, Weill Cornell Medical College, New York, New York 10021, USA.
Abe
Takato
T
Hochrainer
Karin
K
Shimamura
Munehisa
M
Anrather
Josef
J
Racchumi
Gianfranco
G
Zhou
Ping
P
Iadecola
Costantino
C
D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004660:Encephalitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D015870:Gene Expression; D006146:Guanidines / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000378:metabolism*; D053583:Interleukin-1beta; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D018955:CD36 Antigens; D052246:Cyclooxygenase 2 Inhibitors; D006146:Guanidines; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009578:Nitrobenzenes; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C004479:pimagedine