Contact allergens induce in vitro and in vivo the activation of dendritic cells (DC) and Langerhans cells (LC), which includes the up-regulation of surface marker expression (e.g. CD86, CD54) and cytokine production (e.g. TNF-α, IL-1β, IL-8). The mitogen-activated protein kinase (MAPK) pathway also has a crucial role in this activation. However, the extent of MAPK involvement in the IL-8 production during DC/LC activation is not well understood. Earlier, we reported that contact allergens activated THP-1 cells, human monocytic cell line, like LC/DC in vitro. In this study, we further characterize the mechanism of IL-8 production using THP-1 cells as surrogate DCs. First, we evaluated the potential of 23 chemicals with different skin sensitization potencies to predominantly induce IL-8 production in vitro. Next we investigated the role of MAPK signaling and TNF-α, which is known to have autocrine effects on DC activation (e.g., IL-8 production). Inhibition of extracellular signal-regulated kinase (ERK), one of the MAPK pathways, suppressed the IL-8 production induced by both 2,4-dinitrochlorobenzene (DNCB) and nickel sulfate (NiSO4), and inhibition of p38 MAPK, a second MAPK pathway, significantly suppressed IL-8 production induced by only DNCB. Additionally, neutralization of TNF-α activity suppressed IL-8 production in THP-1 cells exposed to DNCB and NiSO4. In conclusion, IL-8 production was predominantly induced in THP-1 cells following allergen stimulation, and MAPK pathways and TNF-α were involved in the IL-8 production induced by DNCB and NiSO4. A better understanding of the mechanism of DC activation in vitro might lead to the clarification of the in vivo skin sensitization mechanism.
2008 The Japanese Society of Toxicology