Limits...
Changes in the Th1:Th2 cytokine bias in pregnancy and the effects of the anti-inflammatory cyclopentenone prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J2.

Sykes L, MacIntyre DA, Yap XJ, Ponnampalam S, Teoh TG, Bennett PR - Mediators Inflamm. (2012)

Bottom Line: The anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-Prostaglandin J(2) (15dPGJ(2)) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor.The percentage of CD4(+) cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ(2) reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2(+ve) cells. 15dPGJ(2) also reduced phospho-p65 in stimulated PBMCs.In summary, 15dPGJ(2) suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

View Article: PubMed Central - PubMed

Affiliation: Parturition Research Group, Department of Surgery and Cancer, Institute of Reproduction and Developmental Biology, Imperial College London, W120NN London, UK.

ABSTRACT
Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2) protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-Prostaglandin J(2) (15dPGJ(2)) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ(2) could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4) synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs) from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ(2) or vehicle control and stimulated with phorbol myristyl acetate (PMA)/ionomycin. The percentage of CD4(+) cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ(2) reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2(+ve) cells. 15dPGJ(2) also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ(2) suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

Show MeSH

Related in: MedlinePlus

Schematic proposal of the Th1 and Th2 balance and the role of CRTH2 and NF-κB. T-helper cell precursors are directed toward committed immunophenotype by the typical Th1 and Th2 interleukins, IFN-γ and IL-4, respectively. Infection or propregnancy hormones such as progesterone can further modulate the Th1/Th2 bias. Based upon our findings and those of others, we propose that 15dPGJ2 maintains a Th2 bias principally through the suppression Th1 interleukins through the inhibition of NF-κB.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368617&req=5

fig5: Schematic proposal of the Th1 and Th2 balance and the role of CRTH2 and NF-κB. T-helper cell precursors are directed toward committed immunophenotype by the typical Th1 and Th2 interleukins, IFN-γ and IL-4, respectively. Infection or propregnancy hormones such as progesterone can further modulate the Th1/Th2 bias. Based upon our findings and those of others, we propose that 15dPGJ2 maintains a Th2 bias principally through the suppression Th1 interleukins through the inhibition of NF-κB.

Mentions: While 15dPGJ2 appears to have no effect on the peripheral Th2 response, the demonstrated inhibition of the Th1 response represents a collective shift toward a Th2 bias, or in other words, an increase in the Th2:Th1 ratio. This has important ramifications for the future design of therapeutic strategies to prevent preterm labour and pregnancy loss (Figure 5). The percentage of CRTH2 positive decidual lymphocytes is far higher, accounting for 10.5% of T lymphocytes and 18% of CD4+ lymphocytes [44]. Exploring the effect of 15dPGJ2 on purified decidual T cells may give rise both Th1 suppression and Th2 cytokine promotion.


Changes in the Th1:Th2 cytokine bias in pregnancy and the effects of the anti-inflammatory cyclopentenone prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J2.

Sykes L, MacIntyre DA, Yap XJ, Ponnampalam S, Teoh TG, Bennett PR - Mediators Inflamm. (2012)

Schematic proposal of the Th1 and Th2 balance and the role of CRTH2 and NF-κB. T-helper cell precursors are directed toward committed immunophenotype by the typical Th1 and Th2 interleukins, IFN-γ and IL-4, respectively. Infection or propregnancy hormones such as progesterone can further modulate the Th1/Th2 bias. Based upon our findings and those of others, we propose that 15dPGJ2 maintains a Th2 bias principally through the suppression Th1 interleukins through the inhibition of NF-κB.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368617&req=5

fig5: Schematic proposal of the Th1 and Th2 balance and the role of CRTH2 and NF-κB. T-helper cell precursors are directed toward committed immunophenotype by the typical Th1 and Th2 interleukins, IFN-γ and IL-4, respectively. Infection or propregnancy hormones such as progesterone can further modulate the Th1/Th2 bias. Based upon our findings and those of others, we propose that 15dPGJ2 maintains a Th2 bias principally through the suppression Th1 interleukins through the inhibition of NF-κB.
Mentions: While 15dPGJ2 appears to have no effect on the peripheral Th2 response, the demonstrated inhibition of the Th1 response represents a collective shift toward a Th2 bias, or in other words, an increase in the Th2:Th1 ratio. This has important ramifications for the future design of therapeutic strategies to prevent preterm labour and pregnancy loss (Figure 5). The percentage of CRTH2 positive decidual lymphocytes is far higher, accounting for 10.5% of T lymphocytes and 18% of CD4+ lymphocytes [44]. Exploring the effect of 15dPGJ2 on purified decidual T cells may give rise both Th1 suppression and Th2 cytokine promotion.

Bottom Line: The anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-Prostaglandin J(2) (15dPGJ(2)) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor.The percentage of CD4(+) cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ(2) reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2(+ve) cells. 15dPGJ(2) also reduced phospho-p65 in stimulated PBMCs.In summary, 15dPGJ(2) suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

View Article: PubMed Central - PubMed

Affiliation: Parturition Research Group, Department of Surgery and Cancer, Institute of Reproduction and Developmental Biology, Imperial College London, W120NN London, UK.

ABSTRACT
Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2) protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-Prostaglandin J(2) (15dPGJ(2)) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ(2) could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4) synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs) from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ(2) or vehicle control and stimulated with phorbol myristyl acetate (PMA)/ionomycin. The percentage of CD4(+) cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ(2) reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2(+ve) cells. 15dPGJ(2) also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ(2) suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

Show MeSH
Related in: MedlinePlus