Cyclooxygenases-1 and -2 differentially modulate leukocyte recruitment into the inflamed brain.
Peripheral leukocyte recruitment in neuroinflammatory conditions can exacerbate brain tissue damage by releasing cytotoxic mediators and by increasing vascular permeability. Cyclooxygenase (COX)-derived prostaglandins promote the migration of several immune cells in vitro, however, the specific roles of COX-1 and -2 on leukocyte recruitment in vivo have not been investigated. To examine the specific effects of COX-1 or COX-2 deficiency on neuroinflammation-induced leukocyte infiltration, we used a model of intracerebroventricular lipopolysaccharide (LPS)-induced neuroinflammation in COX-1(-/-), COX-2(-/-), and their respective wild-type (WT) ((+/+)) mice. After LPS, leukocyte infiltration and inflammatory response were attenuated in COX-1(-/-) and increased in COX-2(-/-) mice, compared with their respective WT controls. This influx of leukocytes was accompanied by a marked disruption of blood-brain barrier and differential expression of chemokines. These results indicate that COX-1 and COX-2 deletion differentially modulate leukocyte recruitment during neuroinflammation, and suggest that inhibition of COX-1 activity is beneficial, whereas COX-2 inhibition is detrimental, during a primary neuroinflammatory response.
Choi
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SH
Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Aid
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Choi
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Bosetti
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D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018925:Chemokines / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000187:drug effects; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2