1. Nuclear Factor-κB Activation and Postischemic Inflammation Are Suppressed in CD36-Null Mice after Middle Cerebral Artery Occlusion
- Author
-
Gianfranco Racchumi, Munehisa Shimamura, Josef Anrather, Ping Zhou, Karin Hochrainer, Alexander Kunz, Costantino Iadecola, and Takato Abe
- Subjects
CD36 Antigens ,Male ,CD36 ,Interleukin-1beta ,Ischemia ,Gene Expression ,Nitric Oxide Synthase Type II ,Inflammation ,Pharmacology ,Guanidines ,Article ,Mice ,medicine ,Animals ,Amino Acid Sequence ,RNA, Messenger ,Scavenger receptor ,Transcription factor ,Nitrobenzenes ,Peroxidase ,Sulfonamides ,Membrane Glycoproteins ,NADPH oxidase ,Cyclooxygenase 2 Inhibitors ,biology ,General Neuroscience ,NF-kappa B ,NADPH Oxidases ,Infarction, Middle Cerebral Artery ,medicine.disease ,NFKB1 ,Mice, Inbred C57BL ,Nitric oxide synthase ,Cyclooxygenase 2 ,Ischemic Attack, Transient ,NADPH Oxidase 2 ,Immunology ,biology.protein ,Encephalitis ,medicine.symptom ,Reactive Oxygen Species - Abstract
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-κB, 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-1β were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-κB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.
- Published
- 2008