title: Phenotypic alterations and cytokine production in THP-1 cells in response to allergens.
abstract: In the induction phase of allergic contact hypersensitivity, dendritic cells (DCs), including Langerhans cells (LCs) present in epidermis, can trigger an efficient T cell response once they have matured in response to an allergen. Upon maturation, DCs have been shown to induce expression of several surface molecules and the up-regulation of cytokine production. We have previously shown that THP-1 cells, human acute monocytic leukemia cell line, can discriminate between allergens and irritants by measuring expression of surface markers, CD86 and CD54, following chemical exposure. At the same time, we have also reported that augmented expression of HLA and CD80, and production of IL-1beta were up-regulated in THP-1 cells when treated with an allergen, 2,4-dinitrochlorobenzene (DNCB). In the present study, we first evaluated whether THP-1 cells induced the phenotypic changes and the production of cytokines, which are observed in the process of DC maturation, when treated with two known allergens, DNCB and nickel sulfate (NiSO(4)), and one irritant (sodium lauryl sulfate (SLS)). Exposure to DNCB and NiSO(4) induced significant augmentation of CD40 and CD83 expression as well as CD86 and CD54. Also, TNF-alpha and IL-8 secretion were markedly induced by DNCB and NiSO(4) in a dose-dependent manner. In addition, DNCB and NiSO(4) augmented CD1a expression and production of IL-6, respectively. On the contrary, SLS did not change any of these markers. We then evaluated a series of chemicals, including six known allergens (e.g., hydroquinone (HQ)) and two non-allergens (e.g., methyl paraben (MP)), in order to investigate the potential increase of CD86, CD54, CD40, and CD83 expression on THP-1 cells, and production of TNF-alpha and IL-8. Indeed, all tested allergens, except eugenol (EU), caused significant increased changes in at least four of the analyzed six markers, while non-allergens did not induce any changes. EU significantly augmented CD86, CD54 and CD40 expression. These results revealed that the wide variety of responses to allergens in THP-1 cells may emulate allergen-induced maturation processes of DCs. It is suggested that THP-1 cells, which could develop several DC-like properties, are suitable for identifying sensitizing potential of chemicals.
authors.affiliation: Safety and Microbial Control Research Center, Kao Corporation, 2606 Akabane, Ichikai-Maich, Haga-Gun Tochigi 321-3497, Japan. miyazawa.masaaki@kao.co.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ito
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000485:Allergens / Q000633:toxicity*; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007509:Irritants / Q000633:toxicity*; D007801:Langerhans Cells / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D010641:Phenotype; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity*; D000097802:CD83 Antigen
chemical_list: D000485:Allergens; D015703:Antigens, CD; D015415:Biomarkers; D019013:CD40 Antigens; D016207:Cytokines; D004137:Dinitrochlorobenzene; D007136:Immunoglobulins; D007509:Irritants; D008562:Membrane Glycoproteins; D009532:Nickel; D012967:Sodium Dodecyl Sulfate; D000097802:CD83 Antigen; C029938:nickel sulfate