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NF-κB Plays a Major Role in the Maturation of Human Dendritic Cells Induced by NiSO4 but not by DNCB

2007; Oxford University Press; Volume: 99; Issue: 2 Linguagem: Inglês

10.1093/toxsci/kfm178

1096-6080

Nadège Ade, Diane Antonios, Saadia Kerdine‐Römer, Fanny Boislève, F Rousset, Marc Pallardy,

RNA Interference and Gene Delivery

Dendritic cell (DC) activation is a critical event for the induction of an immune response to haptens. Although signaling pathways such as mitogen-activated protein kinase (MAPK) family members have been reported to play a role in DC activation by haptens, little is known about the implication of the nuclear factor kappa B (NF-κB) pathway. In this work, we showed that NiSO4 induced the expression of HLA-DR, CD83, CD86, and CD40 and the production of interleukin (IL)-8, IL-6, and IL-12p40 in human DCs, 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 IκB-α leading to the binding of the p65 subunit of NF-κB on specific DNA probes. Inhibition of the NF-κB 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-κB were independently activated by NiSO4 since SB203580 did not inhibit NF-κB activation by NiSO4. Interestingly, we also showed that DNCB inhibited the degradation of IκB-α induced by tumor necrosis factor-α leading to alteration of CD40, HLA-DR, and CD83 expression but not of CD86 and CCR7. Extensive modifications of DC phenotype by NiSO4 in comparison to DNCB are probably the consequence of NF-κB activation by NiSO4 but not by DNCB.