Nickel and DNCB induce CCR7 expression on human dendritic cells through different signalling pathways:: Role of TNF-α and MAPK

被引:96
作者
Boislève, F
Kerdine-Römer, S
Rougier-Larzat, N
Pallardy, M
机构
[1] Univ Paris 11, Fac Pharm, INSERM, UMRS 461, F-92296 Chatenay Malabry, France
[2] Biopredic, Rennes, France
关键词
contact hypersensitivity; hapten; migration; signal transduction;
D O I
10.1111/j.0022-202X.2004.23229.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
After application of haptens on the skin, immature dendritic cells (DC), also named Langerhans cells (LC), migrate to the draining lymph node to sensitize naive T-lymphocytes. Migration of DC involves many factors including the Cys-Cys chemokine receptor, CCR7. We investigated the effects of two well-known haptens, dinitrochlorobenzene (DNCB) and nickel (NiSO4), on the expression of CCR7 on human DC derived from CD34(+) progenitor cells. Both haptens were able to induce CCR7 expression and DC migration in response to Cys-Cys chemokine ligand, CCL19. Since interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha have been shown to participate in LC migration during contact hypersensitivity, we tested the effect of their neutralization on CCR7 expression. Neutralization of IL-1beta activity did not modify CCR7 expression in response to both haptens. CCR7 expression was strongly dependent on TNF-alpha in the case of DNCB, however, neutralization of TNF-alpha only partially reduced CCR7 expression upon NiSO4 treatment. DNCB, NiSO4 and TNF-alpha activated p38 mitogen-activated protein kinases (MAPK) and c-jun N-terminal kinase (JNK). Both p38 MAPK and JNK participated to TNF-alpha production induced by DNCB. Inhibition of both p38 MAPK and JNK affected significantly CCR7 expression upon nickel treatment whereas only inhibition of p38 MAPK but not of JNK downregulated CCR7 in the case of TNF-alpha stimulation. These results suggest that MAPK are necessary for haptens to induce CCR7 expression. NiSO4, however, activates directly CCR7 expression through p38 MAPK and JNK activation whereas DNCB needs TNF-alpha whose secretion is also regulated by p38 MAPK and JNK.
引用
收藏
页码:494 / 502
页数:9
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