Role of MAPK signaling pathway in the activation of dendritic type cell line, THP-1, induced by DNCB and NiSO<sub>4</sub>

Abstract

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-alpha 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 NiSO(4). We found that DNCB and NiSO(4) induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK activation selectively blocked DNCB-induced TNF-alpha release, but not NiSO(4)-induced release. In contrast, inhibition of ERK pathways selectively suppressed NiSO(4)-induced TNF-alpha 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 NiSO(4). In particular, inhibition of p38 MAPK suppressed CD86, CD54, and CD40 expression induced by DNCB and CD86 expression induced by NiSO(4) while inhibition of ERK pathways suppressed CD86, CD54 and CD40 expression induced by DNCB and NiSO(4). These data indicate that both DNCB and NiSO(4) activate p38 MAPK and ERK, and thereby stimulate TNF-alpha release and phenotypic changes through the different signal transduction pathways.