Prostaglandin Receptors of the EP2 and EP4 Subtypes Regulate B Lymphocyte Activation and Differentiation to IGE-Secreting Cells

Fedyk, Eric R.; Harris, Sarah G.; Padilla, Josué; Phipps, Richard P.

doi:10.1007/978-1-4899-1810-9_31

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…Early work suggested that PGE 2 could play an important role in regulating the differentiation of mouse B lymphocytes to IgE secreting cells (55). However, this role was not supported by the report that IgE levels were actually higher in the COX-1 and COX-2 antigen treated animals (23).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Church

Jania

Koller

2012

The Journal of Immunology

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Elevated PGE2 is a hallmark of most inflammatory lesions. This lipid mediator can induce the cardinal signs of inflammation, and the beneficial actions of non-steroidal anti-inflammatory drugs are attributed to inhibition of cyclooxygenase COX-1 and COX-2, enzymes essential in the biosynthesis of PGE2 from arachidonic acid. However, both clinical studies and rodent models suggest that, in the asthmatic lung, PGE2 acts to restrain the immune response and limit physiological change secondary to inflammation. To directly address the role of PGE2 in the lung, we examined the development of disease in mice lacking microsomal prostaglandin E synthase 1 (mPGES1), which converts COX-1/COX-2 derived PGH2 to PGE2. We show that mPGES1 determines PGE2 levels in the naïve lung and is required for increases in PGE2 after ovalbumin (OVA) induced allergy. While loss of either COX-1 or COX-2 increases the disease severity, surprisingly mPGES1 −/− mice show reduced inflammation. However, an increase in serum IgE is still observed in the mPGES1 −/− mice, suggesting that loss of PGE2 does not impair induction of a TH2 response. Furthermore, mPGES1 −/− mice expressing a transgenic OVA-specific T cell receptor are also protected, indicating that PGE2 acts primarily after challenge with inhaled antigen. PGE2 produced by the lung plays the critical role in this response, as loss of lung mPGES1 is sufficient to protect against disease. Together this supports a model in which mPGES1-dependent PGE2 produced by populations of cells native to the lung contributes to the effector phase of some allergic responses.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Church

Jania

Koller

2012

The Journal of Immunology

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“…30,35 In part, this can be attributed to the direct binding of PGE 2 to receptors on B cells. 36 This interaction has been demonstrated to induce the production of germ line ε transcripts that then promote class switching to IgE. 35 This unusual relationship of having both Th-1 and Th-2 cytokines promoting IgG2 responses prompted the hypothesis that, in certain circumstances, PGE 2 enhances rather than inhibits IFN-γ production.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E₂‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma

Tanaka

Barbour

Best

et al. 2003

Journal of Periodontology

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“…In murine systems, it is well established that PGE 2 promotes isotype switching to IgE and IgG1 (19,28). In part, this can be attributed to the direct binding of PGE 2 to receptors on B cells (13). This interaction has been demonstrated to induce the production of germ line ⑀ transcripts that then promote class switching to IgE (27).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2000

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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 (PGE 2 ), 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 PGE 2 or platelet-activating factor (PAF), another lipid cytokine, which can elevate PGE 2 synthesis. Furthermore, IgG2 production was abrogated when cells were treated with indomethacin, a cyclooxygenase inhibitor that blocks the synthesis of PGE 2 , or the PAF antagonists CV3988 and TEPC-15. The effects of indomethacin were completely reversed by PGE 2 , indicating that this is the only prostanoid that is essential for the production of IgG2. Similarly, PGE 2 reversed the effects of a PAF antagonist, suggesting that the effects of PAF are mediated through the induction of PGE 2 synthesis. Together, these data indicate that PGE 2 and PAF are essential for the production of IgG2.Recent results suggest that early-onset periodontitis (EOP) patients have a genetic predisposition to develop disease early in life (22). The clinical manifestations of EOP are variable. Even in the same family, some patients may have a localized form restricted to first molars and incisors (localized juvenile periodontitis [LJP]) and others a severe generalized form. It is likely that these differences in clinical expression are related to several factors, including differences in microbial flora and differences in the host response. Serum total immunoglobulin G2 (IgG2) levels in LJP patients are significantly elevated over those in race-and age-matched controls with no periodontitis (NP controls) (21). Much of this IgG2 antibody is directed against Actinobacillus actinomycetemcomitans serotype b, a putative etiologic agent for EOP, and Porphyromonas gingivalis, which is also associated with EOP (8,20,36,37). The immunodominant antigens of these organisms are the serotype-specific carbohydrates, and, for A. actinomycetemcomitans, the carbohydrate is a high-molecular-weight form of lipopolysaccharide (LPS) (7,8,35,36). Compared to NP subjects, EOP patients frequently have very high titers of IgG2 reactive with the high-molecular-weight A. actinomycetemcomita...

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Prostaglandin Receptors of the EP2 and EP4 Subtypes Regulate B Lymphocyte Activation and Differentiation to IGE-Secreting Cells

Cited by 12 publications

References 26 publications

Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Prostaglandin E₂‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma

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

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Prostaglandin Receptors of the EP2 and EP4 Subtypes Regulate B Lymphocyte Activation and Differentiation to IGE-Secreting Cells

Cited by 12 publications

References 26 publications

Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Prostaglandin E2‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma

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

Contact Info

Product

Resources

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Prostaglandin E₂‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma

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