Asthma and lower airway diseaseProstaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells
Section snippets
Animals
Mice harboring a targeted deletion of both alleles of the ptger2 gene encoding the EP2 receptor were originally generated by Dr Richard Breyer (Vanderbilt University)22 and bred in the University of Michigan Unit for Laboratory Animal Medicine. Eight- to 12-week-old male mice were used for all experiments. Animals were treated according to National Institutes of Health guidelines for the use of experimental animals, with the approval of the University of Michigan Committee for the Use and Care
Enhanced allergic inflammation in EP2−/− animals
PGE2-EP2 signaling has been shown to be immunosuppressive in many different cell types and in vivo models.12, 15 Here we used EP2-deficient (EP2−/−) and EP2-sufficient (WT) mice to assess the importance of endogenous PGE2-EP2 signaling in a model of OVA-induced allergic asthma.24 After sensitization and subsequent airway challenge using the protocol outlined in Fig 1, A, differential cell counts from BALF cytospin preparations revealed higher numbers of both total leukocytes and eosinophils in
Discussion
Exogenous PGE2 has long been known to be a direct bronchodilator29, 30, 31, 32 and to protect against airway inflammatory responses to challenges, such as aspirin33, 34 and allergen.35, 36, 37 However, this abundant prostanoid is also well known to exert pleiotropic effects on immune responses, and its influence on the initiation of the allergic response and the subsequent consequences thereof in a model of allergic asthma remains uncertain. Precedent exists for EP2 mediating suppressive
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Supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, to Z.Z.), American Lung Association Senior Research Fellowships (to Z.Z., K.O., and E.B.), T32 AI007413 and American Heart Association (to R.D.-G.), and National Institutes of Health grants R01 HL94311 and R01 HL58897 (to M.P.-G.), AI065543 (to B.B.M.), AI032302 (to N.W.L.), and HD057176 (to D.M.A.).
Disclosure of potential conflict of interest: Z. Zasłona has received grants from the German Research Foundation and the American Lung Association. R. Domingo-Gonzalez has received grants from the National Institutes of Health (NIH) and the American Heart Association. B. B. Moore has received a grant from the NIH. M. Peters-Golden has received grants from the NIH, the American Lung Association, Nycomed/Takeda, and Actelion; was formerly on the respiratory advisory board for Merck and Company; has consultant arrangements with Nycomed/Takeda, GlaxoSmithKline, and Sanofi-Aventis; has received payment for lectures from Merck and Company; and shares a patent with the University of Michigan on intrapulmonary administration of LTB4 to boost immunity, licensed to Sweden AB, and receives royalties from this patent. The rest of the authors declare that they have no relevant conflicts of interest.