The relationship between CD86 and CD54 proteinexpression and cytotoxicity following stimulation withcontact allergen in THP-1 cells

Abstract

Contact allergens induce the augmentation of cell surface molecules on and release ofcytokines 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 reportedto induce the phenotypic alteration including the production of pro-inflammatory cytokines and augmentationof cell surface molecules especially at sub-toxic doses. However, the relationship between phenotypicalteration and cytotoxicity is not clear yet. The purpose of this study is to understand the relationshipbetween the protein expression and cytotoxicity induced by contact allergens. First, we observedthat the cytotoxicity induced by contact allergens is caused by both apoptosis and necrosis. Apoptosiswas 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 expressionwhen apoptosis induction pathways were inhibited. Based on these findings, we proposed that the proteinexpression and cytotoxicity were controlled independently. Next, oxidative stress was found to be generatedby contact allergens at the early phase, and this regulated the protein expression and cytotoxicityat 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. Theprotein expression was not induced. Altogether, these results suggest that cytotoxicity induced by contactallergens may result in apoptosis and may also be stimulated in parallel with protein expression throughan intracellular signal or signals.