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Genetic deletion of mPGES-1 in mice results in diminished PGE<jats:sub>2<\/jats:sub>production and elevated levels of other prostaglandins after infection. Since PGE<jats:sub>2<\/jats:sub>plays an important immunoregulatory role during bacterial pneumonia we assessed the impact of mPGES-1 deletion in the host defense against pneumococcal pneumonia in vivo and in AMs in vitro. Wild-type (WT) and mPGES-1 knockout (KO) mice were challenged with Streptococcus pneumoniae via the intratracheal route. Compared with WT animals, we observed reduced survival and increased lung and spleen bacterial burdens in mPGES-1 KO mice 24 and 48 h after S. pneumoniae infection. While we found modest differences between WT and mPGES-1 KO mice in pulmonary cytokines, AMs from mPGES-1 KO mice exhibited defective killing of ingested bacteria in vitro that was associated with diminished inducible nitric oxide synthase expression and reduced nitric oxide (NO) synthesis. Treatment of AMs from mPGES-1 KO mice with an NO donor restored bacterial killing in vitro. These results suggest that mPGES-1 plays a critical role in bacterial pneumonia and that genetic ablation of this enzyme results in diminished pulmonary host defense in vivo and in vitro. These results suggest that specific inhibition of PGE<jats:sub>2<\/jats:sub>synthesis by targeting mPGES-1 may weaken host defense against bacterial infections.<\/jats:p>","DOI":"10.1152\/ajplung.00220.2015","type":"journal-article","created":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T17:25:32Z","timestamp":1461950732000},"page":"L1111-L1120","source":"Crossref","is-referenced-by-count":12,"title":["Increased lethality and defective pulmonary clearance of<i>Streptococcus pneumoniae<\/i>in microsomal prostaglandin E synthase-1-knockout mice"],"prefix":"10.1152","volume":"310","author":[{"given":"Jennifer M.","family":"Dolan","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason B.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Disease and Microbiology and 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