Sphingosine kinase inhibitor suppresses dendritic cell migration by regulating chemokine receptor expression and impairing p38 mitogen-activated protein kinase.
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.
Jung
In Duk
ID
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.
Lee
Jun Sik
JS
Kim
Yong Joo
YJ
Jeong
Young-Il
YI
Lee
Chang-Min
CM
Lee
Min Goo
MG
Ahn
Soon-Choel
SC
Park
Yeong-Min
YM
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
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