title: Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2.
abstract: Prostanoids generated by COX-2 are involved in the regulation of inflammation but their exact role in the innate immune response has not been defined. We investigated whether COX-2 is involved in host defense against Pseudomonas aeruginosa pneumonia. In vitro studies, in a macrophage cell line, showed that cytotoxic strain of P aeruginosa (PA103) induced significant COX-2 protein expression and enzymatic function. In vivo data showed that infection with PA103 increased COX-2 protein production in whole lung tissue compared to mice that were infected with mutant bacteria that lack ExoU (DeltaU) or ExoU and ExoT (DeltaUT). COX-2(-/-) mice had accentuated clearance of cytotoxic P. aeruginosa from the lungs. We further tested the effects of COX-2 products such as prostaglandin E(2) on the function of phagocytic cells. Our studies indicate that prostaglandin E(2) may be involved through interacting with the EP2 receptors in modulating the host response because treatment of macrophages with prostaglandin E(2) suppressed production of reactive oxygen species. Furthermore there was enhanced bacterial clearance in EP2 receptor(-/-) mice compared to the wild-type controls. Thus it is possible that inhibition of COX-2 or EP2 receptors could be an effective adjunctive treatment for severe or resistant P. aeruginosa pneumonia.
authors.affiliation: Department of Veterans Affairs, Jesse Brown VA Hospital, Chicago, IL 60612, USA. sadikot@uic.edu
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
authors.forename: Heng
authors.initials: H
authors.lastname: Zeng
authors.forename: Anser C
authors.initials: AC
authors.lastname: Azim
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: John W
authors.initials: JW
authors.lastname: Christman
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011453:Prostaglandins / Q000096:biosynthesis; D011552:Pseudomonas Infections / Q000201:enzymology / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D051546:Cyclooxygenase 2