title: The relationship between CD86 and CD54 protein expression and cytotoxicity following stimulation with contact allergen in THP-1 cells.
abstract: 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.
authors.affiliation: Kao Corporation, 2606 Akabane, Haga-Gun, Tochigi 321-3497, Japan. nukada.yuko@kao.co.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nukada
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ito
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishiyama
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000633:toxicity; D000485:Allergens / Q000633:toxicity*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051940:B7-2 Antigen / Q000378:metabolism*; D061945:Caspase Inhibitors; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000633:toxicity; D005054:Eugenol / Q000633:toxicity; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D019344:Lactic Acid / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects; D011435:Propyl Gallate / Q000633:toxicity; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity
chemical_list: D000485:Allergens; D000590:Amino Acid Chloromethyl Ketones; D051940:B7-2 Antigen; C497964:CD86 protein, human; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004137:Dinitrochlorobenzene; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D018799:Intercellular Adhesion Molecule-1; D019344:Lactic Acid; D012967:Sodium Dodecyl Sulfate; D005054:Eugenol; D011435:Propyl Gallate; D000079:Acetaldehyde; C013192:phenylacetaldehyde