Prostaglandin E2and IL-4 Provide Naive CD4+T Cells with Distinct Inhibitory Signals for the Priming of IFN-γ Production

Abe, Nobutaka; Katamura, Kenji; Shimizu, N; Fukui, Tetsuya; Kiyomasu, Takahiro; Iio, Jun; Ueno, Hideki; Tai, Guihua; Mayumi, Mitsuhumi; Furusho, Kenshi

doi:10.1006/cimm.1997.1180

Cited by 36 publications

(13 citation statements)

References 36 publications

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“…These reports and our findings indicate that cAMP regulates Th1/Th2 balance at a number of different stages. Interestingly, a representative Th2 activator, IL-4, does not participate in the elevation of cAMP (47). This finding indicates that PGE 2 engages Th2 activation in a quite different way from IL-4.…”

Section: Discussionmentioning

confidence: 87%

Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC

Kuroda

Sugiura

Okada

et al. 2001

The Journal of Immunology

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PGE2 has been known to suppress Th1 responses. We studied the role of PGE2 in two representative chemokines, macrophage-derived chemokine (MDC) and IFN-inducible protein-10, production by LPS- or CD40-stimulated spleen cells. The production of MDC, one of the ligands for CCR4 preferentially expressed on Th2, was enhanced in nonstimulated, LPS-, CD40-, or CD3-stimulated spleen cells by the pretreatment with PGE2, while the production of IFN-inducible protein-10, a representative ligand for CXC chemokine receptor 3 expressed on Th1, was suppressed. MDC production was also enhanced by IL-4, IL-5, and intracellular cAMP-elevating agents such as dibutyryl cAMP and 3-isobutyl-1-methylxanthine, and the effect of IL-4, IL-5, and PGE2 was additive. However, the pretreatment with IL-6, IL-10, or TGF-β, or the neutralization of IFN-γ or IL-12 had no effect on MDC production. B cells, macrophages, and dendritic cells were main producers of MDC, while T cells produced only a small amount of MDC. MDC production by B cells was equally stimulated by LPS and anti-CD40 Ab, while that by macrophages and dendritic cells was more markedly stimulated by anti-CD40 Ab, and PGE2 further enhanced MDC production by these stimulated cells. These results indicate that PGE2 regulates Th1/Th2-related chemokine production by B cells, macrophages, and dendritic cells, and that this is a new function of PGE2 for the regulation of Th2 immune responses at the induction and activation stages.

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Section: Discussionmentioning

confidence: 87%

Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC

Kuroda

Sugiura

Okada

et al. 2001

The Journal of Immunology

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“…Involvement of cAMP in the regulation of Th1/Th2 cytokine balance has been known for a long time: activation of T lymphocytes at the background of cAMPincreasing factors (Abe et al, 1997;Benbernou et al, 1997) or membrane-penetrating cAMP analogs (Benbernou et al, 1997;Shin et al, 1998;Wu et al, 1998) decreases IFNγ expression (Abe et al, 1997;Benbernou et al, 1997;Shin et al, 1998) and increases the levels of IL-4 and IL-10 (Benbernou et al, 1997;Wu et al, 1998). The reverse effect of cAMP on the expression of Th1 and Th2 cytokine genes can be mediated both by differential regulation of transcription factors, primarily, nuclear factor of activated T cells (NFAT), nuclear factor κB (NFκB), and activator protein 1 (AP-1) and by different sensitivity of cytokine genes to the same nuclear factors.…”

Section: Resultsmentioning

confidence: 99%

Reproductive Hormones in the Control of Th1/Th2 Cytokine Balance

Куклина

Shirshev

2005

Biol Bull Russ Acad Sci

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Individual and combined effects of chorionic gonadotropin (CG), estradiol, and progesterone on the production of IFN γ and IL-4 by human peripheral blood lymphocytes was studied in vitro together with certain intracellular mechanisms underlying the hormonal effects. High CG dose (100 IU/ml) proved to significantly decrease IFN γ level in the T cell culture supernatant, although this effect was not observed at the background of steroid hormones. In contrast, progesterone (100 ng/ml) increased IFN γ production by activated T lymphocytes but proved inefficient in a physiological combination with CG and estradiol. IL-4 production was almost doubled by all studied hormones and their combinations, which considerably decreased the IFN γ /IL-4 ratio in the culture. Inhibition analysis employing blockers of cAMP-dependent protein kinase (H-89) and L-type calcium channels (verapamil) as well as an antagonist of progesterone nuclear receptors (RU-486) demonstrated that the inhibitory (for IFN γ ) and stimulatory (for IL-4) effects of CG were mediated by cAMP, while the effects of steroid hormones on the production of these cytokines were realized through genomic and non-genomic mechanisms (the latter mechanisms were largely mediated by L-type calcium channel regulation). Overall, the studied reproductive hormones could efficiently regulate synthesis of the main Th1 (IFN γ ) and Th2 (IL-4) cytokines by T lymphocytes and seem to play the key role in changing the pregnancy-specific pattern of secreted cytokines.

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“…19 Studies in both human and murine systems indicate that interaction of PGE 2 with naive T cells and accessory cells induces the Th-2 phenotype. [30][31][32] These T cells produce interleukin-4 (IL-4), IL-5, and the other Th-2 cytokines that promote the production of IgE and IgG1. 30 It is also known that DCs are critical for stimulating naive T cells and that incubating DCs with PGE 2 promotes Th-2 responses.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that DCs are critical for stimulating naive T cells and that incubating DCs with PGE 2 promotes polarization toward Th-2 responses. 30,31 However, it is also known that monocyte-derived DCs have a strong tendency to polarize toward Th-1 24 and that Th-1-associated factors from accessory cells including IL-12, IL-18, IL-1α, and IL-1β, are necessary for optimal IgG2 responses (references 10 and 21 and unpublished data). However, it has been reported that subnanomolar concentrations of PGE 2 can act on primed Th-1 cells and enhance the production of IFNγ.…”

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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Prostaglandin E2and IL-4 Provide Naive CD4+T Cells with Distinct Inhibitory Signals for the Priming of IFN-γ Production

Cited by 36 publications

References 36 publications

Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC

Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC

Reproductive Hormones in the Control of Th1/Th2 Cytokine Balance

Prostaglandin E₂‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma

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Prostaglandin E2and IL-4 Provide Naive CD4+T Cells with Distinct Inhibitory Signals for the Priming of IFN-γ Production

Cited by 36 publications

References 36 publications

Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC

Prostaglandin E2 Up-Regulates Macrophage-Derived Chemokine Production but Suppresses IFN-Inducible Protein-10 Production by APC

Reproductive Hormones in the Control of Th1/Th2 Cytokine Balance

Prostaglandin E2‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma

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Prostaglandin E₂‐Mediated Regulation of Immunoglobulin G2 via Interferon Gamma