The relationship between CD86 and CD54 protein expression and cytotoxicity following stimulation with contact allergen in THP-1 cells.

Contact allergens induce the augmentation of cell surface molecules on and release of cytokines from Langerhans cells (LC) in skin sensitization. THP-1 and U937 cell lines, surrogates of LC, were used as analytical tools of this phenomenon recently. In THP-1 cells, contact allergens are reported to induce the phenotypic alteration including the production of pro-inflammatory cytokines and augmentation of cell surface molecules especially at sub-toxic doses. However, the relationship between phenotypic alteration and cytotoxicity is not clear yet. The purpose of this study is to understand the relationship between the protein expression and cytotoxicity induced by contact allergens. First, we observed that the cytotoxicity induced by contact allergens is caused by both apoptosis and necrosis. Apoptosis was preferentially confirmed in stimulation with contact allergens, but non-allergen sodium lauryl sulfate (SLS) hardly induced apoptosis. Moreover, there was no effect to augmentation of protein expression when apoptosis induction pathways were inhibited. Based on these findings, we proposed that the protein expression and cytotoxicity were controlled independently. Next, oxidative stress was found to be generated by contact allergens at the early phase, and this regulated the protein expression and cytotoxicity at least partially. Finally, the humoral factors from dead cells induced by dinitrochlorobenzene (DNCB) were exposed to fresh THP-1 cells to confirm whether protein expression depended on cytotoxicity. The protein expression was not induced. Altogether, these results suggest that cytotoxicity induced by contact allergens may result in apoptosis and may also be stimulated in parallel with protein expression through an intracellular signal or signals.