Regulation of Immunoglobulin G2 Production by Prostaglandin E2and Platelet-Activating Factor

Patients with localized juvenile periodontitis (LJP) have elevated levels of immunoglobulin G2 (IgG2) in their sera. This is also observed in vitro when peripheral blood leukocytes from LJP patients are stimulated with pokeweed mitogen. In previous studies, we showed that lymphocytes from subjects with no periodontitis (NP subjects) produced substantial amounts of IgG2 when they were cultured with monocytes from LJP patients (LJP monocytes). These observations indicate that monocytes or monocyte-derived mediators are positive regulators of the production of IgG2. The present study was initiated to determine if secreted factors from LJP monocytes were capable of enhancing IgG2 production and to determine if prostaglandin E2 (PGE2 ), which LJP monocytes produce at elevated levels, enhances IgG2 production. Experiments in a transwell system and with monocyte-conditioned media indicated that cell-cell contact was not necessary for LJP monocytes to augment the production of IgG2 by T and B cells from NP subjects. Moreover, the production of IgG2 was selectively induced by the addition of PGE2 or platelet-activating factor (PAF), another lipid cytokine, which can elevate PGE2 synthesis. Furthermore, IgG2 production was abrogated when cells were treated with indomethacin, a cyclooxygenase inhibitor that blocks the synthesis of PGE2 , or the PAF antagonists CV3988 and TEPC-15. The effects of indomethacin were completely reversed by PGE2 , indicating that this is the only prostanoid that is essential for the production of IgG2. Similarly, PGE2 reversed the effects of a PAF antagonist, suggesting that the effects of PAF are mediated through the induction of PGE2 synthesis. Together, these data indicate that PGE2 and PAF are essential for the production of IgG2.