The activation of dendritic cells (DC), including Langerhans cells (LC) that reside within the epidermis, is a critical event in the induction phase of allergic contact hypersensitivity. Although recently, p38 mitogen-activated protein kinase (MAPK) has been reported to play a role in the activation of DC induced by allergens, the signaling pathways involved in this process have yet to be determined. We previously found that THP-1 cells have a high capacity to induce TNF-α release and CD86, CD54, and CD40 expression following allergen treatment; reflecting in vitro allergen-induced DC activation during skin sensitization. In this study, we investigated the signaling pathways in THP-1 cells activated by two representative allergens, DNCB and NiSO4. We found that DNCB and NiSO4 induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK activation selectively blocked DNCB-induced TNF-α release, but not NiSO4-induced release. In contrast, inhibition of ERK pathways selectively suppressed NiSO4-induced TNF-α release but not DNCB-induced release. In addition, we found that the inhibition of p38 MAPK and ERK pathways caused a selective inhibition of CD86, CD54, and/or CD40 expression following treatment with DNCB or NiSO4. In particular, inhibition of p38 MAPK suppressed CD86, CD54, and CD40 expression induced by DNCB and CD86 expression induced by NiSO4 while inhibition of ERK pathways suppressed CD86, CD54 and CD40 expression induced by DNCB and NiSO4. These data indicate that both DNCB and NiSO4 activate p38 MAPK and ERK, and thereby stimulate TNF-α release and phenotypic changes through the different signal transduction pathways.
2008 The Japanese Society of Toxicology