{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:20:40Z","timestamp":1774437640289,"version":"3.50.1"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Entamoeba histolytica<\/jats:italic>pathogenesis in the colon occurs in a stepwise fashion. It begins with colonization of the mucin layer, which is followed by stimulation of a proinflammatory response that causes nonspecific tissue damage that may facilitate parasite invasion of the underlying colonic mucosa. Unfortunately, the parasite and\/or host factors that stimulate a proinflammatory response in the gut are poorly understood. In this study, we found that live<jats:italic>E. histolytica<\/jats:italic>or secretory or proteins (SP) and soluble ameba components (SAP) can markedly increase interleukin-8 (IL-8) mRNA expression and protein production in colonic epithelial cells. The IL-8-stimulating molecule produced by live amebae was identified as prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) as trophozoites treated with cyclooxygenase inhibitors inhibited the biosynthesis of PGE<jats:sub>2<\/jats:sub>and eliminated IL-8 production induced by live parasites or ameba components. Moreover, using specific prostaglandin EP2 and EP4 receptor agonists and antagonists, we found that PGE<jats:sub>2<\/jats:sub>binds exclusively through EP4 receptors in colonic epithelial cells to stimulate IL-8 production. Silencing of EP4 receptors with EP4 small interfering RNA completely eliminated SP- and SAP-induced IL-8 production. These studies identified bioactive PGE<jats:sub>2<\/jats:sub>as a one of the major virulence factors produced by<jats:italic>E. histolytica<\/jats:italic>that can stimulate the potent neutrophil chemokine and activator IL-8, which can trigger an acute host inflammatory response. Thus, the induction of IL-8 production in response to<jats:italic>E. histolytica<\/jats:italic>-derived PGE<jats:sub>2<\/jats:sub>may be a mechanism that explains the initiation and amplification of acute inflammation associated with intestinal amebiasis.<\/jats:p>","DOI":"10.1128\/iai.00645-08","type":"journal-article","created":{"date-parts":[[2008,8,19]],"date-time":"2008-08-19T00:34:20Z","timestamp":1219106060000},"page":"5158-5163","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":44,"title":["Prostaglandin E<sub>2<\/sub>Produced by<i>Entamoeba histolytica<\/i>Binds to EP4 Receptors and Stimulates Interleukin-8 Production in Human Colonic Cells"],"prefix":"10.1128","volume":"76","author":[{"given":"Indranil","family":"Dey","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kris","family":"Chadee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01309.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4522-4529.2005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60509-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0300-9475.2004.01440.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70285-4"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040008"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01383-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(94)00143-X"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1835863100"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118161"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.2.318"},{"key":"e_1_3_2_13_2","unstructured":"Reference deleted."},{"key":"e_1_3_2_14_2","first-page":"679","volume":"12","year":"2007","unstructured":"Garc\u00eda-Zepeda, E. 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