NF- Kappa B Plays a Major Role in the Maturation of Human Dendritic Cells Induced by NiSO sub(4) but not by DNCB

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- Kappa B) pathway. In this work, we showed that NiSO sub(4) 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. NiSO sub(4) but not DNCB was able to activate the degradation of I Kappa B- alpha leading to the binding of the p65 subunit of NF- Kappa B on specific DNA probes. Inhibition of the NF- Kappa B pathway using BAY 11-7085 prevents both CD40 and HLA-DR expression and cytokine production induced by NiSO sub(4). However, BAY 11-7085 only partially inhibited CD86 and CD83 expression induced by NiSO sub(4). In addition, p38 MAPK and NF- Kappa B were independently activated by NiSO sub(4) since SB203580 did not inhibit NF- Kappa B activation by NiSO sub(4). Interestingly, we also showed that DNCB inhibited the degradation of I Kappa B- alpha induced by tumor necrosis factor- alpha leading to alteration of CD40, HLA-DR, and CD83 expression but not of CD86 and CCR7. Extensive modifications of DC phenotype by NiSO sub(4) in comparison to DNCB are probably the consequence of NF- Kappa B activation by NiSO sub(4) but not by DNCB.