PMID- 16313356 OWN - NLM STAT- MEDLINE DCOM- 20060113 LR - 20181113 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 116 IP - 4 DP - 2005 Dec TI - Leukotrienes modulate cytokine release from dendritic cells. PG - 418-28 AB - Leukotriene B(4) (LTB(4)) and cysteinyl leukotrienes (CysLTs) are known as potent mediators of inflammation, whereas their role in the regulation of adaptive immunity remains poorly characterized. Dendritic cells (DCs) are specialized antigen-presenting cells, uniquely capable to initiate primary immune responses. We have found that zymosan, but not lipopolysaccharide (LPS) stimulates murine bone marrow-derived dendritic cells (BM-DCs) to produce large amounts of CysLTs and LTB(4) from endogenous substrates. A selective inhibitor of leukotriene synthesis MK886 as well as an antagonist of the high affinity LTB(4) receptor (BLT(1)) U-75302 slightly inhibited zymosan-, but not LPS-stimulated interleukin (IL)-10 release from BM-DCs. In contrast, U-75302 increased zymosan-stimulated release of IL-12 p40 by approximately 23%. Pre-treatment with transforming growth factor-beta1 enhanced both stimulated leukotriene synthesis and the inhibitory effect of U-75302 and MK886 on IL-10 release from DCs. Consistent with the effects of leukotriene antagonists, exogenous LTB(4) enhanced LPS-stimulated IL-10 release by approximately 39% and inhibited IL-12 p40 release by approximately 22%. Both effects were mediated by the BLT(1) receptor. Ligands of the high affinity CysLTs receptor (CysLT(1)), MK-571 and LTD(4) had little or no effect on cytokine release. Agonists of the nuclear LTB(4) receptor peroxisome proliferator-activated receptor-alpha, 8(S)-hydroxyeicosatetraenoic acid and 5,8,11,14-eicosatetraynoic acid, inhibited release of both IL-12 p40 and IL-10. Our results indicate that both autocrine and paracrine leukotrienes may modulate cytokine release from DCs, in a manner that is consistent with previously reported T helper 2-polarizing effects of leukotrienes. FAU - Jozefowski, Szczepan AU - Jozefowski S AD - Department of Immunology, Jagiellonian University School of Medicine, Krakow, Poland. szjozefowski@poczta.onet.pl FAU - Biedron, Rafal AU - Biedron R FAU - Bobek, Malgorzata AU - Bobek M FAU - Marcinkiewicz, Janusz AU - Marcinkiewicz J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Cytokines) RN - 0 (Leukotrienes) RN - 0 (Lipopolysaccharides) RN - 0 (Ltb4r1 protein, mouse) RN - 0 (Receptors, Leukotriene B4) RN - 0 (Receptors, Purinergic P2) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 130068-27-8 (Interleukin-10) RN - 1HGW4DR56D (Leukotriene B4) RN - 9010-72-4 (Zymosan) SB - IM MH - Animals MH - Bone Marrow Cells/immunology MH - Cells, Cultured MH - Cytokines/*metabolism MH - Dendritic Cells/*immunology MH - Interleukin-10/biosynthesis MH - Leukotriene B4/immunology MH - Leukotrienes/biosynthesis/*immunology MH - Lipopolysaccharides/immunology MH - Mice MH - Mice, Inbred CBA MH - Receptors, Leukotriene B4/immunology MH - Receptors, Purinergic P2/immunology MH - Transforming Growth Factor beta/immunology MH - Transforming Growth Factor beta1 MH - Zymosan/immunology PMC - PMC1802435 EDAT- 2005/11/30 09:00 MHDA- 2006/01/18 09:00 PMCR- 2006/12/01 CRDT- 2005/11/30 09:00 PHST- 2005/11/30 09:00 [pubmed] PHST- 2006/01/18 09:00 [medline] PHST- 2005/11/30 09:00 [entrez] PHST- 2006/12/01 00:00 [pmc-release] AID - IMM2241 [pii] AID - 10.1111/j.1365-2567.2005.02241.x [doi] PST - ppublish SO - Immunology. 2005 Dec;116(4):418-28. doi: 10.1111/j.1365-2567.2005.02241.x.