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Cyclooxygenases-1 and -2 differentially modulate leukocyte recruitment into the inflamed brain

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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