title: Sphingosine kinase inhibitor suppresses dendritic cell migration by regulating chemokine receptor expression and impairing p38 mitogen-activated protein kinase.
abstract: The migration of dendritic cells (DCs) to secondary lymphoid organs plays a crucial role in the initiation of adaptive immune responses. Although lipopolysaccharide enhances chemokine receptor 7 (CCR7) expression on DCs, the second signal for the migration of DCs toward the chemokine CCL19 remains unknown. In this study, we show that sphingosine kinase inhibitor (SKI) inhibits the migration of DCs toward CCL19 through the down-regulation of CCR7. Inhibition of p38 mitogen-activated protein kinase (MAPK) activation by SKI may be responsible for the SKI-mediated effects on the regulation of chemokine receptor expression. Impairment of DC migration by the inhibition of p38 MAPK and down-regulation of CCR7 expression may contribute to the protective effects of SKI in DC-related disorders. These results suggest that sphingosine kinase-mediated signalling plays a role in the innate and adaptive immune responses by altering DC migration.
authors.affiliation: Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation & Regulation, Medical Research Institute, Pusan National University, College of Medicine, Busan, Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.forename: Soon-Choel
authors.initials: SC
authors.lastname: Ahn
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000276:immunology; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D054415:Chemokine CCL19; D019742:Chemokines, CC; D004791:Enzyme Inhibitors; D016753:Interleukin-10; D018664:Interleukin-12; D008070:Lipopolysaccharides; D017853:Phosphotransferases (Alcohol Group Acceptor); D019707:Receptors, Chemokine; D048051:p38 Mitogen-Activated Protein Kinases; D000099157:Sphingosine Kinase; C515461:Ccl19 protein, mouse