{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:56:18Z","timestamp":1791204978364,"version":"4.1.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Streptococcus pyogenes (Group A Streptococcus; GAS) is a major cause of severe postpartum sepsis, a re-emerging cause of maternal morbidity and mortality worldwide. Immunological alterations occur during pregnancy to promote maternofetal tolerance, which may increase the risk for puerperal infection. PGE2 is an immunomodulatory lipid that regulates maternofetal tolerance, parturition, and innate immunity. The extent to which PGE2 regulates host immune responses to GAS infections in the context of endometritis is unknown. To address this, both an in vivo mouse intrauterine (i.u.) GAS infection model and an in vitro human macrophage\u2013GAS interaction model were used. In C57BL\/6 mice, i.u. GAS inoculation resulted in local and systemic inflammatory responses and triggered extensive changes in the expression of eicosanoid pathway genes. The i.u. administration of PGE2 increased the mortality of infected mice, suppressed local IL-6 and IL-17A levels, enhanced neutrophilic inflammation, reduced uterine macrophage populations, and increased bacterial dissemination. A role for endogenous PGE2 in the modulation of antistreptococcal host defense was suggested, because mice lacking the genes encoding the microsomal PGE2 synthase-1 or the EP2 receptor were protected from death, as were mice treated with the EP4 receptor antagonist, GW627368X. PGE2 also regulated GAS\u2013macrophage interactions. In GAS-infected human THP-1 (macrophage-like) cells, PGE2 inhibited the production of MCP-1 and TNF-\u03b1 while augmenting IL-10 expression. PGE2 also impaired the phagocytic ability of human placental macrophages, THP-1 cells, and mouse peritoneal macrophages in vitro. Exploring the targeted disruption of PGE2 synthesis and signaling to optimize existing antimicrobial therapies against GAS may be warranted.<\/jats:p>","DOI":"10.4049\/jimmunol.1300786","type":"journal-article","created":{"date-parts":[[2013,8,3]],"date-time":"2013-08-03T05:06:52Z","timestamp":1375506412000},"page":"2457-2465","source":"Crossref","is-referenced-by-count":22,"title":["Intrauterine Group A Streptococcal Infections Are Exacerbated by Prostaglandin E2"],"prefix":"10.1093","volume":"191","author":[{"given":"Katie L","family":"Mason","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Rogers","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyara M","family":"Soares","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo 14040-903,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Bani-Hashemi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Erb Downward","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalen","family":"Agnew","sequence":"additional","affiliation":[{"name":"Diagnostic Center for Population and Animal Health, Michigan State University , Lansing, MI 48910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Peters-Golden","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason B","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"},{"name":"Department of Microbiology and Immunology, University of Michigan School of Medicine , Ann Arbor, MI 48109"},{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan School of Medicine , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J","family":"Crofford","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Center for the Advancement of Women\u2019s Health, University of Kentucky , Lexington, KY 40506"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Aronoff","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System , Ann Arbor, MI 48109"},{"name":"Department of Microbiology and Immunology, University of Michigan School of Medicine , Ann Arbor, MI 48109"},{"name":"Reproductive Sciences Program, University of Michigan School of Medicine , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"key":"2025032405264275900_r1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/QCO.0b013e328339257c","article-title":"Maternal sepsis: epidemiology, etiology and outcome","volume":"23","author":"van Dillen","year":"2010","journal-title":"Curr. 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