ToxSci Advance Access published online on July 16, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm178
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NF-
B Plays a Major Role in the Maturation of Human Dendritic Cells Induced by NiSO4 But Not by DNCB
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* Univ Paris-Sud, UMR-S 749, 92296 Châtenay-Malabry, France
INSERM, 92296 Châtenay-Malabry, France (nadege.ade{at}u-psud.fr, diane.antonios{at}u-psud.fr, saadia.kerdine{at}u-psud.fr, fanyboisleve{at}hotmail.com)
L'Oréal Recherche, 92117 Clichy-La Garenne, France (frousset{at}rd.loreal.com)
¶ Corresponding author : Marc Pallardy, INSERM UMR-S 749 and Toxicology, Faculté de Pharmacie, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex France, Phone : 33-1-46-83-54-92, Fax : 33-1-46-83-54-96, e-mail : marc.pallardy{at}u-psud.fr
Received May 14, 2007; revision received July 2, 2007; accepted July 3, 2007
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Abstract |
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Dendritic cell activation is a critical event for the induction of an immune response to haptens. Although signalling pathways such as MAPK family members have been reported to play a role in dendritic cell activation by haptens, little is known about the implication of the NF-
B pathway. In this work, we showed that NiSO4 induced the expression of HLA-DR, CD83, CD86 and CD40 and the production of IL-8, IL6 and IL-12p40 in human dendritic cells whereas DNCB induced mainly the expression of CD83 and CD86 and the production of IL-8. NiSO4 but not DNCB was able to activate the degradation of IB-
leading to the binding of the p65 subunit of NF-B on specific DNA probes. Inhibition of the NF-B pathway using BAY 11-7085, prevents both CD40 and HLA-DR expression and cytokine production induced by NiSO4. However, BAY 11-7085 only partially inhibited CD86 and CD83 expression induced by NiSO4. In addition, p38 MAPK and NF-B were independently activated by NiSO4 since SB203580 did not inhibit NF-B activation by NiSO4. Interestingly, we also showed that DNCB inhibited the degradation of IB- induced by TNF- leading to alteration of CD40, HLA-DR and CD83 expression but not of CD86 and CCR7. Extensive modifications of dendritic cell phenotype by NiSO4 in comparison to DNCB are probably the consequence of NF-B activation by NiSO4 but not by DNCB.
Key Words: contact hypersensitivity; NF-B; hapten; dendritic cells.
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