NF-kappaB plays a major role in the maturation of human dendritic cells induced by NiSO(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-kappaB) pathway. In this work, we showed that NiSO(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(4) but not DNCB was able to activate the degradation of IkappaB-alpha leading to the binding of the p65 subunit of NF-kappaB on specific DNA probes. Inhibition of the NF-kappaB pathway using BAY 11-7085 prevents both CD40 and HLA-DR expression and cytokine production induced by NiSO(4). However, BAY 11-7085 only partially inhibited CD86 and CD83 expression induced by NiSO(4). In addition, p38 MAPK and NF-kappaB were independently activated by NiSO(4) since SB203580 did not inhibit NF-kappaB activation by NiSO(4). Interestingly, we also showed that DNCB inhibited the degradation of IkappaB-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(4) in comparison to DNCB are probably the consequence of NF-kappaB activation by NiSO(4) but not by DNCB.
Ade
Nadège
N
Univ Paris-Sud, INSERM, 92296 Châtenay-Malabry, France.
Antonios
Diane
D
Kerdine-Romer
Saadia
S
Boisleve
Fanny
F
Rousset
Françoise
F
Pallardy
Marc
M
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007136:Immunoglobulins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000097802:CD83 Antigen
D015703:Antigens, CD; D018952:Antigens, CD34; D051940:B7-2 Antigen; D016207:Cytokines; D004137:Dinitrochlorobenzene; D006684:HLA-DR Antigens; D051550:I-kappa B Kinase; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009532:Nickel; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000097802:CD83 Antigen; C497964:CD86 protein, human; C029938:nickel sulfate