PMID- 19220324 OWN - NLM STAT- MEDLINE DCOM- 20090616 LR - 20211020 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 156 IP - 1 DP - 2009 Apr TI - Interaction between prostaglandin D and chemoattractant receptor-homologous molecule expressed on Th2 cells mediates cytokine production by Th2 lymphocytes in response to activated mast cells. PG - 126-33 LID - 10.1111/j.1365-2249.2008.03871.x [doi] AB - The mechanisms by which immunologically activated mast cells stimulate the production of proinflammatory cytokines by T helper type 2 (Th2) lymphocytes were investigated in a human cell culture system. Supernatants collected from cord blood-derived mast cells after treatment with immunoglobulin E (IgE)/anti-IgE contained an activity that stimulated the production of interleukin (IL)-4, IL-5 and IL-13 (both mRNA and protein) by Th2 lymphocytes. This activity was not detected in supernatants from unactivated mast cells and its production was inhibited by treatment of activated mast cells with the cyclo-oxygenase inhibitor diclofenac. The concentration of diclofenac used inhibited completely the production of prostaglandin D(2) (PGD(2)) but did not inhibit the release of histamine or leukotriene C(4). The effect of supernatants from activated mast cells was mimicked by exogenous PGD(2) at concentrations similar to those detected in the cultures of activated mast cells, and addition of exogenous PGD(2) to supernatants from diclofenac-treated mast cells restored their ability to stimulate Th2 cytokine production. The ability of the mast cell supernatants to stimulate production of Th2 cytokines was not affected by addition of diclofenac to the Th2 cells directly, indicating that the production, but not the action, of the factor was sensitive to diclofenac treatment. Inhibition of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) abolished the effect of the mast cell supernatants on Th2 cytokine production. These data indicate that mast cells have the ability to stimulate Th2 cells to elaborate cytokines independently of T cell receptor activation or co-stimulation and this response is mediated by PGD(2) acting upon CRTH2 expressed by Th2 cells. FAU - Xue, L AU - Xue L AD - Oxagen Ltd, Abingdon, Oxon, UK. xue@oxagen.co.uk FAU - Barrow, A AU - Barrow A FAU - Pettipher, R AU - Pettipher R LA - eng PT - Journal Article DEP - 20090211 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Prostaglandin) RN - RXY07S6CZ2 (Prostaglandin D2) RN - XZF106QU24 (prostaglandin D2 receptor) SB - IM MH - Cells, Cultured MH - Culture Media, Conditioned MH - Cytokines/*biosynthesis/genetics MH - Gene Expression Regulation/immunology MH - Humans MH - Mast Cells/*immunology MH - Prostaglandin D2/immunology/*metabolism MH - RNA, Messenger/analysis MH - Receptors, Immunologic/immunology/*metabolism MH - Receptors, Prostaglandin/immunology/*metabolism MH - Th2 Cells/*immunology PMC - PMC2673750 EDAT- 2009/02/18 09:00 MHDA- 2009/06/17 09:00 PMCR- 2010/04/01 CRDT- 2009/02/18 09:00 PHST- 2009/02/18 09:00 [entrez] PHST- 2009/02/18 09:00 [pubmed] PHST- 2009/06/17 09:00 [medline] PHST- 2010/04/01 00:00 [pmc-release] AID - CEI3871 [pii] AID - 10.1111/j.1365-2249.2008.03871.x [doi] PST - ppublish SO - Clin Exp Immunol. 2009 Apr;156(1):126-33. doi: 10.1111/j.1365-2249.2008.03871.x. Epub 2009 Feb 11.