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Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E2 critically depends on interleukin‐2
Abstract
Prostaglandin E 2 (PGE 2) favors T helper type 2 (Th2)‐like cytokine secretion profiles in murine and human CD4+ T cells by inhibiting the production of the Th1‐associated cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) and up‐regulating the production of the Th2‐associated cytokines IL‐4 and IL‐5 in a dose‐dependent way. However, the potent inhibition of IL‐2 production by PGE 2 seems to be in contrast with the simultaneous up‐regulation of IL‐4 and IL‐5 production, because the induction of these cytokines requires IL‐2. We, therefore, investigated to which extent the net modulatory effect of PGE 2 is determined by the availability of IL‐2. To this aim, we examined the effects of PGE 2 on the cytokine secretion profiles of a panel of human Th0 clones upon stimulation via different activation pathways, resulting either in high or low IL‐2 production. The differential modulation of Th1 and Th2 cytokines by PGE 2 was observed only upon modes of stimulation resulting in high IL‐2 production. When IL‐2 production was low, PGE 2 inhibited the secretion of all four cytokines. These different modulation patterns were directly related to the IL‐2 availability, because (i) neutralizing antibody to IL‐2 abrogated the up‐regulatory effect of PGE 2 on IL‐4 and IL‐5 secretion in experiments with high endogenous IL‐2 levels, (ii) lack of differential cytokine modulation by PGE 2 in conditions with low levels of endogenous IL‐2 could be restored with exogenous IL‐2, and (iii) cell viability was comparable in all conditions. These results demonstrate that the net modulatory effect of PGE 2 on the cytokine secretion profile of T cells critically depends on the availability of IL‐2. Since this parameter varies with the experimental conditions and the T cell population studied, this finding may explain why certain immune responses may be either up‐ or down‐regulated by PGE 2 under different conditions.
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Cited by
Prescott, S. L., Macaubas, C., Holt, B. J., Smallacombe, T. B., Loh, R., Sly, P. D., & Holt, P. G. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.10.4730 · Cited by 788
Yao, C., Sakata, D., Esaki, Y., Li, Y., Matsuoka, T., Kuroiwa, K., Sugimoto, Y., & Narumiya, S. (2009) · Nature Medicine · doi:10.1038/nm.1968 · Cited by 566
Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors
Kawahara, K., Hohjoh, H., Inazumi, T., Tsuchiya, S., & Sugimoto, Y. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.07.008 · Cited by 488
Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases
Tsuge, K., Inazumi, T., Shimamoto, A., & Sugimoto, Y. (2019) · International Immunology · doi:10.1093/intimm/dxz021 · Cited by 263
An exposome perspective: Early-life events and immune development in a changing world
Renz, H., Holt, P. G., Inouye, M., Logan, A. C., Prescott, S. L., & Sly, P. D. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.05.015 · Cited by 226
Metadata
- Authors
- Hilkens, C. M. U., Vermeulen, H., van Neerven, R. J. J., Snijdewint, F. G. M., Wierenga, E. A., & Kapsenber, M. L.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 1995-01
- Volume
- 25
- Issue
- 1
- Pages
- 59-63
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2120580301
- Cited by
- 179
- References
- 0
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E2 critically depends on interleukin‐2. https://app.cochat.ai/papers/10.1002/eji.1830250112
- The paper
- Hilkens, C. M. U., Vermeulen, H., van Neerven, R. J. J., Snijdewint, F. G. M., Wierenga, E. A., & Kapsenber, M. L. (1995). Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E2 critically depends on interleukin‐2. European Journal of Immunology. https://doi.org/10.1002/eji.1830250112
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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