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Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells.
J Immunol. 2005 Nov 15; 175(10):6531-6.JI

Abstract

PGD2, produced by mast cells, has been detected in high concentrations at sites of allergic inflammation. It can stimulate vascular and other inflammatory responses by interaction with D prostanoid receptor (DP) and chemoattractant receptor-like molecule expressed on Th2 cells (CRTH2) receptors. A significant role for PGD2 in mediating allergic responses has been suggested based on the observation that enhanced eosinophilic lung inflammation and cytokine production is apparent in the allergen-challenged airways of transgenic mice overexpressing human PGD2 synthase, and PGD2 can enhance Th2 cytokine production in vitro from CD3/CD28-costimulated Th2 cells. In the present study, we investigated whether PGD2 has the ability to stimulate Th2 cytokine production in the absence of costimulation. At concentrations found at sites of allergic inflammation, PGD2 preferentially elicited the production of IL-4, IL-5, and IL-13 by human Th2 cells in a dose-dependent manner without affecting the level of the anti-inflammatory cytokine IL-10. Gene transcription peaked within 2 h, and protein release peaked approximately 8 h after stimulation. The effect of PGD2 was mimicked by the selective CRTH2 agonist 13,14-dihydro-15-keto-PGD2 but not by the selective DP agonist BW245C, suggesting that the stimulation is mediated by CRTH2 and not DP. Ramatroban, a dual CRTH2/thromboxane-like prostanoid receptor antagonist, markedly inhibited Th2 cytokine production induced by PGD2, while the selective thromboxane-like prostanoid receptor antagonist SQ29548 was without effect. These data suggest that PGD2 preferentially up-regulates proinflammatory cytokine production in human Th2 cells through a CRTH2-dependent mechanism in the absence of any other costimulation and highlight the potential utility of CRTH2 antagonists in the treatment of allergic diseases.

Authors+Show Affiliations

Oxagen Limited, Abingdon, Oxon, United Kingdom. l.xue@oxagen.co.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16272307

Citation

Xue, Luzheng, et al. "Prostaglandin D2 Causes Preferential Induction of Proinflammatory Th2 Cytokine Production Through an Action On Chemoattractant Receptor-like Molecule Expressed On Th2 Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 175, no. 10, 2005, pp. 6531-6.
Xue L, Gyles SL, Wettey FR, et al. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol. 2005;175(10):6531-6.
Xue, L., Gyles, S. L., Wettey, F. R., Gazi, L., Townsend, E., Hunter, M. G., & Pettipher, R. (2005). Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. Journal of Immunology (Baltimore, Md. : 1950), 175(10), 6531-6.
Xue L, et al. Prostaglandin D2 Causes Preferential Induction of Proinflammatory Th2 Cytokine Production Through an Action On Chemoattractant Receptor-like Molecule Expressed On Th2 Cells. J Immunol. 2005 Nov 15;175(10):6531-6. PubMed PMID: 16272307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. AU - Xue,Luzheng, AU - Gyles,Shân L, AU - Wettey,Frank R, AU - Gazi,Lucien, AU - Townsend,Elizabeth, AU - Hunter,Michael G, AU - Pettipher,Roy, PY - 2005/11/8/pubmed PY - 2006/1/4/medline PY - 2005/11/8/entrez SP - 6531 EP - 6 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 175 IS - 10 N2 - PGD2, produced by mast cells, has been detected in high concentrations at sites of allergic inflammation. It can stimulate vascular and other inflammatory responses by interaction with D prostanoid receptor (DP) and chemoattractant receptor-like molecule expressed on Th2 cells (CRTH2) receptors. A significant role for PGD2 in mediating allergic responses has been suggested based on the observation that enhanced eosinophilic lung inflammation and cytokine production is apparent in the allergen-challenged airways of transgenic mice overexpressing human PGD2 synthase, and PGD2 can enhance Th2 cytokine production in vitro from CD3/CD28-costimulated Th2 cells. In the present study, we investigated whether PGD2 has the ability to stimulate Th2 cytokine production in the absence of costimulation. At concentrations found at sites of allergic inflammation, PGD2 preferentially elicited the production of IL-4, IL-5, and IL-13 by human Th2 cells in a dose-dependent manner without affecting the level of the anti-inflammatory cytokine IL-10. Gene transcription peaked within 2 h, and protein release peaked approximately 8 h after stimulation. The effect of PGD2 was mimicked by the selective CRTH2 agonist 13,14-dihydro-15-keto-PGD2 but not by the selective DP agonist BW245C, suggesting that the stimulation is mediated by CRTH2 and not DP. Ramatroban, a dual CRTH2/thromboxane-like prostanoid receptor antagonist, markedly inhibited Th2 cytokine production induced by PGD2, while the selective thromboxane-like prostanoid receptor antagonist SQ29548 was without effect. These data suggest that PGD2 preferentially up-regulates proinflammatory cytokine production in human Th2 cells through a CRTH2-dependent mechanism in the absence of any other costimulation and highlight the potential utility of CRTH2 antagonists in the treatment of allergic diseases. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16272307/Prostaglandin_D2_causes_preferential_induction_of_proinflammatory_Th2_cytokine_production_through_an_action_on_chemoattractant_receptor_like_molecule_expressed_on_Th2_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16272307 DB - PRIME DP - Unbound Medicine ER -