Abstract
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.
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Acknowledgements
We thank Dr Robert Langenbach (Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health) for providing COX-1−/−, COX-2−/−, and their WT mice. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.
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Choi, SH., Aid, S., Choi, U. et al. Cyclooxygenases-1 and -2 differentially modulate leukocyte recruitment into the inflamed brain. Pharmacogenomics J 10, 448–457 (2010). https://doi.org/10.1038/tpj.2009.68
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DOI: https://doi.org/10.1038/tpj.2009.68
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