{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:42:29Z","timestamp":1760920949203,"version":"build-2065373602"},"reference-count":0,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Patients with localized aggressive periodontitis (LAgP) produce elevated levels of IgG2 both in vivo and in vitro. Responses to the periodontitis\u2010associated pathogens <jats:italic>Actinobacillus actinomycetemcomitans<\/jats:italic> and <jats:italic>Porphyromonas gingivalis<\/jats:italic> are dominated by IgG2, and these IgG2 responses are associated with reduced extent and severity of disease. Little is known about regulation of the IgG2 subclass, although prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) (a mediator known to polarize responses toward Th\u20102) and interferon (IFN)\u2010\u03b3 (a Th\u20101 mediator) both promote IgG2 production. This unusual relationship prompted the hypothesis that, in certain circumstances, PGE<jats:sub>2<\/jats:sub> enhances rather than inhibits IFN\u2010\u03b3 production.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> To test this hypothesis, indomethacin (IND)\u2010treated peripheral blood mononuclear cell (PBL) cultures from healthy volunteers were stimulated with pokeweed mitogen (PWM), and the cultures were manipulated by adding PGE<jats:sub>2<\/jats:sub>, rIFN\u2010\u03b3, rIL\u20101\u03b1, rIL\u20101\u03b2, rIL\u20106, or rIL\u201012. Production of IgG1, IgG2, IFN\u2010\u03b3, and PGE<jats:sub>2<\/jats:sub> was monitored by enzyme\u2010linked immunosorbent assay.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Indomethacin treatment inhibited IgG1 and IgG2 production, and PGE<jats:sub>2<\/jats:sub> restored both immunoglobulins in PWMstimulated cultures. Remarkably, addition of IFN\u2010\u03b3 also restored IND\u2010suppressed IgG2 but not IgG1. In contrast, addition of rIL (interleukin)\u20101\u03b1, rIL\u20101\u03b2, rIL\u20106, or rIL\u201012 did not restore IgG2 responses. Furthermore, IND suppressed IFN\u2010\u03b3 production and PGE<jats:sub>2<\/jats:sub> increased IFN\u2010\u03b3 levels. Kinetic studies indicate that PGE<jats:sub>2<\/jats:sub> production occurred on the first day of culture, followed by IFN\u2010\u03b3 two days later.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> These findings support the concept that in certain circumstances, PGE<jats:sub>2<\/jats:sub> production can lead to increased IFN\u2010\u03b3 and that this IFN\u2010\u03b3 selectively promotes IgG2 responses. These data suggest that the elevated PGE<jats:sub>2<\/jats:sub> observed in LAgP patients may contribute to increased IFN\u2010\u03b3 production and help explain elevated IgG2 responses. <jats:italic>J Periodontol 2003;74:771\u2010779<\/jats:italic>.<\/jats:p>","DOI":"10.1902\/jop.2003.74.6.771","type":"journal-article","created":{"date-parts":[[2005,2,2]],"date-time":"2005-02-02T07:40:58Z","timestamp":1107330058000},"page":"771-779","source":"Crossref","is-referenced-by-count":12,"title":["Prostaglandin E<sub>2<\/sub>\u2010Mediated Regulation of Immunoglobulin G2 via Interferon Gamma"],"prefix":"10.1002","volume":"74","author":[{"given":"Shigehisa","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne E.","family":"Barbour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Al M.","family":"Best","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey A.","family":"Schenkein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"Tew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,3]]},"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2003.74.6.771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T14:01:07Z","timestamp":1760882467000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2003.74.6.771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["10.1902\/jop.2003.74.6.771"],"URL":"https:\/\/doi.org\/10.1902\/jop.2003.74.6.771","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"type":"print","value":"0022-3492"},{"type":"electronic","value":"1943-3670"}],"subject":[],"published":{"date-parts":[[2003,3]]}}}