{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:58:45Z","timestamp":1790506725421,"version":"4.1.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>Prostaglandin E&lt;sub&gt;2&lt;\/sub&gt; (PGE&lt;sub&gt;2&lt;\/sub&gt;), an arachidonic acid metabolite regulating a broad range of physiological activities, is an important modulator of the severity of infection caused by &lt;i&gt;Streptococcus pyogenes&lt;\/i&gt;. Here, we investigated the role of streptococcal cytolysin S (SLS) and streptococcal cytolysin O (SLO) in the induction of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of prostaglandins, in in vitro cultured macrophages and during in vivo infection. Macrophages were infected with &lt;i&gt;S. pyogenes &lt;\/i&gt;wild type or with the isogenic mutant strains deficient in SLS (&amp;#x0394;SLS), SLO (&amp;#x0394;SLO), or both (&amp;#x0394;SLS\/&amp;#x0394;SLO), and the expression of COX-2 was determined at the transcriptional and the protein level. The results indicated that &lt;i&gt;S. pyogenes &lt;\/i&gt;induced expression of COX-2 and concomitant synthesis of PGE&lt;sub&gt;2&lt;\/sub&gt; in macrophages mediated by the synergistic activity of both SLS and SLO, and involved calcium and the PKC\/JNK signaling pathway. These results were validated using recombinant cytolysins. In a murine skin infection model, COX-2-positive cells were found more abundant at the site of &lt;i&gt;S. pyogenes &lt;\/i&gt;wild-type infection than at the site of infection with &amp;#x0394;SLS\/&amp;#x0394;SLO mutant strain. These findings suggest that inhibitory targeting of SLS and SLO could ameliorate the adverse effects of high levels of prostaglandins during &lt;i&gt;S. pyogenes &lt;\/i&gt;infection.<\/jats:p>","DOI":"10.1159\/000479153","type":"journal-article","created":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T21:01:21Z","timestamp":1502917281000},"page":"587-597","source":"Crossref","is-referenced-by-count":14,"title":["Induction of Cyclooxygenase 2 by &lt;b&gt;&lt;i&gt;Streptococcus pyogenes &lt;\/i&gt;&lt;\/b&gt;Is Mediated by Cytolysins"],"prefix":"10.1159","volume":"9","author":[{"given":"Ulrike","family":"Blaschke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Beineke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Klemens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Goldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2017,8,17]]},"container-title":["Journal of Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/479153","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/479153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:42:53Z","timestamp":1745426573000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000479153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,11,23]]}},"URL":"https:\/\/doi.org\/10.1159\/000479153","archive":["Portico"],"relation":{},"ISSN":["1662-811X","1662-8128"],"issn-type":[{"value":"1662-811X","type":"print"},{"value":"1662-8128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}