Cyclooxygenase-1 and -2 in brains of patients who died with sporadic Creutzfeldt-Jakob disease.
Cyclooxygenases (COXs) mediate inflammation, immunomodulation, blood flow, apoptosis, and fever in various diseases of the brain. Whereas COX-2 is cytokine inducible, COX-1 is expressed by macrophages/microglial cells that accumulate in pathological foci. We analyzed the localization of COX-1 and COX-2 in postmortem cortex slices of eight patients who died with sporadic Creutzfeldt-Jakob disease (CJD) and four neuropathologically unaltered controls by immunohistochemical double-labeling, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blotting experiments. In healthy brains, COX-1 was expressed by single macrophages/microglial cells and COX-2 by disseminated neurons. In patients with CJD, significantly (p = 0.0195) more COX-1-expressing macrophages/microglial cells were detected adjacent to neurons. COX-2 expression was predominantly observed in neurons, and their number was significantly higher (p < 0.0001) compared to controls. RT-PCR and Western blotting revealed more COX-1 and COX-2 mRNA and protein in one CJD patient than in one control patient. These data show that accumulation of COX-1-expressing macrophages/microglial cells and COX-2-expressing neurons might represent important regulatory mechanisms in the complex process of neuronal degeneration in CJD patients.
Deininger
Martin H
MH
Institute of Brain Research, University of Tuebingen Medical School, Tuebingen, Germany. martin.deininger@uni-tuebingen.de
Bekure-Nemariam
Kubrom
K
Trautmann
Katrin
K
Morgalla
Matthias
M
Meyermann
Richard
R
Schluesener
Hermann J
HJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human