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Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk.

Xue L, Fergusson J, Salimi M, Panse I, Ussher JE, Hegazy AN, Vinall SL, Jackson DG, Hunter MG, Pettipher R, Ogg G, Klenerman P - J. Allergy Clin. Immunol. (2014)

Bottom Line: The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production.The receptors for these mediators are drug targets in the treatment of allergic diseases, and hence understanding their interaction is likely to have clinical implications.Blockade of PGD2 and LTE4 was tested by using TM30089, an antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells, and montelukast, an antagonist of cysteinyl leukotriene receptor 1.

View Article: PubMed Central - PubMed

Affiliation: Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: luzheng.xue@ndm.ox.ac.uk.

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PGD2 and LTE4 modulate gene transcription of cytokines, chemokines, and surface receptors in TH2 cells determined by means of microarray (A and B) or PCR array (C). Fig 4, A, Venn diagram and heat map showing the number and distribution of genes significantly regulated. Fig 4, B and C, Strongly upregulated genes. P < .05 (n = 3).
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fig4: PGD2 and LTE4 modulate gene transcription of cytokines, chemokines, and surface receptors in TH2 cells determined by means of microarray (A and B) or PCR array (C). Fig 4, A, Venn diagram and heat map showing the number and distribution of genes significantly regulated. Fig 4, B and C, Strongly upregulated genes. P < .05 (n = 3).

Mentions: To focus on gene regulation potentially relevant to T cell–mediated diseases, we next analyzed the genes encoding cytokines, chemokines, their receptors, and cluster of differentiation (CD) molecules detected by the microarray (Fig 4). A total of 95 of these genes were significantly modulated, most of them upregulated (Fig 4, A, and see Table E2 in this article's Online Repository at www.jacionline.org), most significantly the cytokines and chemokines. Although some of these effects were induced by PGD2 alone (eg, IL26, IL1RL1, and CCR4) or LTE4 alone (eg, CCL3, CCL3L1, CCL3L3, and CCL4L2), most were driven by their combination. In addition to type 2 cytokine genes, the expression of many other genes was also synergistically enhanced by the combination treatment (Fig 4, B). A number of genes were downregulated (see Table E2), notably transcription of GPR44, the gene for CRTH2 (CD294), which was downregulated by 2.4-fold by PGD2 alone and 3.8-fold by combination treatment. Importantly, these microarray data were largely confirmed also by using a PCR array assay for human common cytokines, including 84 cytokine genes, among which approximately 30 showed significant changes (see Table E3 in this article's Online Repository at www.jacionline.org), although some effects (IL10 and IL21) were only detected by using the PCR array (Fig 4, C).


Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk.

Xue L, Fergusson J, Salimi M, Panse I, Ussher JE, Hegazy AN, Vinall SL, Jackson DG, Hunter MG, Pettipher R, Ogg G, Klenerman P - J. Allergy Clin. Immunol. (2014)

PGD2 and LTE4 modulate gene transcription of cytokines, chemokines, and surface receptors in TH2 cells determined by means of microarray (A and B) or PCR array (C). Fig 4, A, Venn diagram and heat map showing the number and distribution of genes significantly regulated. Fig 4, B and C, Strongly upregulated genes. P < .05 (n = 3).
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Related In: Results  -  Collection

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fig4: PGD2 and LTE4 modulate gene transcription of cytokines, chemokines, and surface receptors in TH2 cells determined by means of microarray (A and B) or PCR array (C). Fig 4, A, Venn diagram and heat map showing the number and distribution of genes significantly regulated. Fig 4, B and C, Strongly upregulated genes. P < .05 (n = 3).
Mentions: To focus on gene regulation potentially relevant to T cell–mediated diseases, we next analyzed the genes encoding cytokines, chemokines, their receptors, and cluster of differentiation (CD) molecules detected by the microarray (Fig 4). A total of 95 of these genes were significantly modulated, most of them upregulated (Fig 4, A, and see Table E2 in this article's Online Repository at www.jacionline.org), most significantly the cytokines and chemokines. Although some of these effects were induced by PGD2 alone (eg, IL26, IL1RL1, and CCR4) or LTE4 alone (eg, CCL3, CCL3L1, CCL3L3, and CCL4L2), most were driven by their combination. In addition to type 2 cytokine genes, the expression of many other genes was also synergistically enhanced by the combination treatment (Fig 4, B). A number of genes were downregulated (see Table E2), notably transcription of GPR44, the gene for CRTH2 (CD294), which was downregulated by 2.4-fold by PGD2 alone and 3.8-fold by combination treatment. Importantly, these microarray data were largely confirmed also by using a PCR array assay for human common cytokines, including 84 cytokine genes, among which approximately 30 showed significant changes (see Table E3 in this article's Online Repository at www.jacionline.org), although some effects (IL10 and IL21) were only detected by using the PCR array (Fig 4, C).

Bottom Line: The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production.The receptors for these mediators are drug targets in the treatment of allergic diseases, and hence understanding their interaction is likely to have clinical implications.Blockade of PGD2 and LTE4 was tested by using TM30089, an antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells, and montelukast, an antagonist of cysteinyl leukotriene receptor 1.

View Article: PubMed Central - PubMed

Affiliation: Oxford NIHR Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: luzheng.xue@ndm.ox.ac.uk.

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Related in: MedlinePlus