{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:27:30Z","timestamp":1791844050130,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T00:00:00Z","timestamp":1450224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Upon stimulation, neutrophils release their nuclear contents called neutrophil extracellular traps (NETs), which contain unfolded chromatin and lysosomal enzymes. NETs have been demonstrated to play a critical role in host defence, although the role of PGE<jats:sub>2<\/jats:sub>, a bioactive substance generated in inflammatory tissues, in the formation of NETs remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The effects of PGE<jats:sub>2<\/jats:sub>, agonists and antagonists of its receptors, and modulators of the cAMP\u2013PKA pathway on the formation of NETs were examined <jats:italic>in vitro<\/jats:italic> in isolated neutrophils and <jats:italic>in vivo<\/jats:italic> in a newly established mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>PGE<jats:sub>2<\/jats:sub> inhibited PMA\u2010induced NET formation <jats:italic>in vitro<\/jats:italic> through EP<jats:sub>2<\/jats:sub> and EP<jats:sub>4<\/jats:sub> G\u03b1s\u2010coupled receptors. Incubation with a cell\u2010permeable cAMP analogue, dibutyryl cAMP, or various inhibitors of a cAMP\u2010degrading enzyme, PDE, also suppressed NET formation. In the assay established here, where an agarose gel was s.c. implanted in mice and NET formation was detected on the surface of the gel, the extent of the NET formed was inhibited in agarose gels containing rolipram, a PDE4 inhibitor, and butaprost, an EP<jats:sub>2<\/jats:sub> receptor agonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>PGE<jats:sub>2<\/jats:sub> inhibits NET formation through the production of cAMP. These findings will contribute to the development of novel treatments for NETosis\u2010related diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13373","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T22:39:08Z","timestamp":1445985548000},"page":"319-331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Prostaglandin E<sub>2<\/sub> inhibits neutrophil extracellular trap formation through production of cyclic AMP"],"prefix":"10.1111","volume":"173","author":[{"given":"Kyosuke","family":"Shishikura","sequence":"first","affiliation":[{"name":"The Department of Molecular and Cellular Biology Institute of Development, Aging and Cancer, Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Horiuchi","sequence":"additional","affiliation":[{"name":"The Department of Molecular and Cellular Biology Institute of 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