{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:02:41Z","timestamp":1787767361046,"version":"build-2784847793"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T00:00:00Z","timestamp":1448582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T00:00:00Z","timestamp":1448582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prostacyclin synthase (PGIS) and microsomal prostaglandin E synthase-1 (mPGES-1) are prostaglandin (PG) terminal synthases that function downstream of inducible cyclooxygenase (COX)-2 in the PGI<jats:sub>2<\/jats:sub> and PGE<jats:sub>2<\/jats:sub> biosynthetic pathways, respectively. mPGES-1 has been shown to be involved in various COX-2-related diseases such as inflammatory diseases and cancers, but it is not yet known how PGIS is involved in these COX-2-related diseases. Here, to clarify the pathophysiological role of PGIS, we investigated the phenotypes of PGIS and mPGES-1 individual knockout (KO) or double KO (DKO) mice. The results indicate that a thioglycollate-induced exudation of leukocytes into the peritoneal cavity was suppressed by the genetic-deletion of PGIS. In the PGIS KO mice, lipopolysaccharide-primed pain nociception (as assessed by the acetic acid-induced writhing reaction) was also reduced. Both of these reactions were suppressed more effectively in the PGIS\/mPGES-1 DKO mice than in the PGIS KO mice. On the other hand, unlike mPGES-1 deficiency (which suppressed azoxymethane-induced colon carcinogenesis), PGIS deficiency up-regulated both aberrant crypt foci formation at the early stage of carcinogenesis and polyp formation at the late stage. These results indicate that PGIS and mPGES-1 cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis and that PGIS-derived PGI<jats:sub>2<\/jats:sub> has anti-carcinogenic effects.<\/jats:p>","DOI":"10.1038\/srep17376","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T11:01:07Z","timestamp":1448622067000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1"],"prefix":"10.1038","volume":"5","author":[{"given":"Yuka","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Kamiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Kamiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konomi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moe","family":"Akatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihito","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kuwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntaro","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,27]]},"reference":[{"key":"BFsrep17376_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1146\/annurev.biochem.69.1.145","volume":"69","author":"WL Smith","year":"2000","unstructured":"Smith, W. L., DeWitt, D. L. & Garavito, R. M. Cyclooxygenases: structural, cellular and molecular biology. Annu. Rev. Biochem. 69, 145\u2013182 (2000).","journal-title":"Annu. Rev. Biochem."},{"key":"BFsrep17376_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1146\/annurev.med.57.121304.131253","volume":"58","author":"YI Cha","year":"2007","unstructured":"Cha, Y. I. & DuBois R. N. NSAIDs and cancer prevention: targets downstream of COX-2. Annu. Rev. Med. 58, 239\u2013252 (2007).","journal-title":"Annu. Rev. Med."},{"key":"BFsrep17376_CR3","doi-asserted-by":"publisher","first-page":"5821","DOI":"10.1021\/cr2002992","volume":"111","author":"WL Smith","year":"2011","unstructured":"Smith, W. L., Urade, Y. & Jakobsson, P. J. Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem. Rev. 111, 5821\u20135865 (2011).","journal-title":"Chem. 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Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis. J. Bio. Chem. 278, 19396\u201319405 (2003).","journal-title":"J. Bio. Chem"},{"key":"BFsrep17376_CR7","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.biochi.2010.02.007","volume":"92","author":"S Hara","year":"2010","unstructured":"Hara, S. et al. Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models. Biochimie 92, 651\u2013659 (2010).","journal-title":"Biochimie"},{"key":"BFsrep17376_CR8","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1124\/pr.59.3.1","volume":"59","author":"B Samuelsson","year":"2007","unstructured":"Samuelsson, B., Morgenstern, R. & Jakobsson, P. J. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol. Rev. 59, 207\u2013224 (2007).","journal-title":"Pharmacol. 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