Cysteinyl-leukotriene receptor type 1 expression and function is down-regulated during monocyte-derived dendritic cell maturation with zymosan: involvement of IL-10 and prostaglandins.
TLRs sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). DCs have been shown to produce leukotrienes and, conversely, leukotrienes are known to modulate several DC functions. In this study, we examined the modulation of expression and function of cysteinyl-leukotriene receptor type 1 (CysLT1) on human monocyte-derived DCs during their differentiation and subsequent maturation with zymosan, a TLR2 agonist. Maturation of DCs with zymosan reduced CysLT1 mRNA levels and protein expression in a time-dependent fashion and was associated with a diminution of functional responsiveness to leukotriene D(4) as assessed by intracellular calcium mobilization, CCL2 and CCL3 production, and chemotaxis. The effect of zymosan was mediated by both TLR2 and dectin-1 activation. Zymosan also induced a rapid expression of cyclooxygenase-2 and the production of PGE(2) and IL-10. Addition of an anti-IL-10 neutralizing Ab or inhibitors of cyclooxygenase greatly reduced the ability of zymosan to down-regulate CysLT1 expression. Down-regulation of CysLT1 expression by zymosan could be reproduced by a combination of IL-10 and PGE(2), and was dependent on MAPK activation. Taken together, our findings indicate that zymosan down-regulates CysLT1 expression in DCs with consequently reduced functional responsiveness of the cells to leukotriene D(4) stimulation. This effect is partially dependent on an endogenous production of PGs and IL-10 by DCs.
Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Maryse
M
Thivierge
Jana
J
Stankova
Marek
M
Rola-Pleszczynski
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015232:Dinoprostone / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology; D000099181:Dectin-1
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D016753:Interleukin-10; D037181:Lectins, C-Type; D017998:Leukotriene D4; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D018077:Receptors, Leukotriene; D011994:Recombinant Proteins; D051195:Toll-Like Receptor 2; D015054:Zymosan; D000099181:Dectin-1; C111835:CCL2 protein, human; C515429:CCL3 protein, human; C508609:IL10 protein, human; C495342:TLR2 protein, human; C496540:PTGS2 protein, human; C083169:leukotriene D4 receptor