Role of TNF-α and extracellular ATP in THP-1 cell activation following allergen exposure

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概要

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• Dendritic cells (DCs), including Langerhans cells (LCs), play a critical role in the induction phase of allergic contact hypersensitivity. Following exposure to chemical allergens in the skin, LCs undergo a maturation process leading to the up-regulation of expression of co-stimulatory molecules, such as CD86, CD54 and CD40. Our previous study revealed that chemical allergens induce phenotype alterations (e.g., CD86, CD54 and CD40) and cytokine production (TNF-α and IL-8) in THP-1 cells that possibly reflect the maturation of dendritic cells during skin sensitization. However, the physiological signals for phenotypic alterations by chemical allergens are still not fully understood. Therefore, in this study, we investigated the effect of TNF-α and extracellular ATP on THP-1 cell activation induced by chemical allergens. Kinetic studies revealed that TNF-α and IL-8 release occurred in a time-dependent manner with release of two cytokines beginning at 3hr post-exposure to well-known haptens, DNCB and NiSO_4. While recombinant human TNF-α augmented CD54 and CD40 expression in a dose-dependent manner, rhTNF-α did not increase CD86 expression. Furthermore, neutralization of TNF-α activity strongly inhibited CD54 and CD40 expression induced by allergens. On the contrary, extracellular ATP induced the up-regulation of both CD86 and CD54 expression. In the presence of the P2 receptor antagonist suramin, the up-regulation of CD86 and CD54 expression by allergens was in part suppressed. Therefore, we postulate that not only TNF-α but also extracellular ATP may contribute to cell activation following allergen stimulation, which might reflect the mechanism by which DCs respond to allergens.

• 日本トキシコロジー学会の論文
• 2008-02-15

著者

• Sakaguchi Hitoshi

  Safety Science Research Laboratories, Kao Corporation

• Miyazawa Masaaki

  Kao Corporation Safety Science Research Laboratories

• Nukada Yuko

  Kao Corporation, Safety Science Research Laboratories

• Kosaka Nanae

  Kao Corporation, Safety Science Research Laboratories

• Ito Yuichi

  Kao Corporation, Safety Science Research Laboratories

• Sakaguchi Hitoshi

  Kao Corporation, Safety Science Research Laboratories

• Nishiyama Naohiro

  Kao Corporation, Safety Science Research Laboratories

• Suzuki Hiroyuki

  Kao Corporation, Product Quality Management Division

• Nishiyama Naohiro

  Kao Corporation

• Sakaguchi Hitoshi

  Kao Corporation

• Nukada Yuko

  Kao Corporation

• Ito Yuichi

  Kao Corporation

• Kosaka Nanae

  Kao Corporation

• Suzuki Hiroyuki

  Kao Corporation Product Quality Management Division

• Miyazawa Masaaki

  Kao Corporation

関連論文

• Assessment of the human Cell Line Activation Test (h-CLAT) for Skin Sensitization ; Results of the First Japanese Inter-laboratory Study
• Inter-laboratory study of short time exposure (STE) test for predicting eye irritation potential of chemicals and correspondence to globally harmonized system (GHS) classification
• Results of a Japanese ring study of a Human Cell Line Activation Test (h-CLAT) for predicting skin sensitization potential (1st report)
• Production of IL-8 in THP-1 cells following contact allergen stimulation via mitogen-activated protein kinase activation or tumor necrosis factor-α production
• Role of TNF-α and extracellular ATP in THP-1 cell activation following allergen exposure
• Role of MAPK signaling pathway in the activation of dendritic type cell line, THP-1, induced by DNCB and NiSO_4
• Role of mitogen-activated protein kinase in CD86/CD54 expression induced by contact sensitizers on THP-1 cells
• The response pattern of THP-1 cells to allergens and mechanisms of allergen-induced THP-1 cell activation
• Effects of pre-culture conditions on the human Cell Line Activation Test (h-CLAT) results : Results of the 4^ Japanese inter-laboratory study
• A study on serum difference on test results in the human Cell Line Activation Test (h-CLAT) : Results of 3^ Japanese inter-laboratory study
• A Study of the Criteria for Selection of THP-1 Cells in the Human Cell Line Activation Test (h-CLAT) : Results of 2^ Japanese Inter-laboratory Study
• Review of an alternative to animal testing for safety evaluation of Quasi-drug
• Classification for skin sensitization potency using human Cell Line Activation Test (h-CLAT)
• Evaluation of h-CLAT (in vitro skin sensitization test) based on 100 known chemicals
• Evaluation of eye irritation potential of 114 chemicals and correspondence to GHS classification using in vitro Short Time Exposure (STE) test
• An inter-laboratory study of Short Time Exposure (STE) test for predicting eye irritation potential of personal care products
• The relationship between CD86 and CD54 protein expression and cytotoxicity following stimulation with contact allergen in THP-1 cells
• Cell-based in vitro skin sensitization methods
• In vitro skin sensitization test
• The relationship between CD86 and CD54 protein expression and cytotoxicity following stimulation with contact allergen in THP-1 cells
• The Japanese Ring Study of a Human Cell Line Activation Test (h-CLAT) for Predicting Skin Sensitization Potential (7^ Report) : Evaluation of Volatile, Poorly Soluble Fragrance Materials
• The Japanese Ring Study of a Human Cell Line Activation Test (h-CLAT) for Predicting Skin Sensitization Potential (6^ Report) : A Study for Evaluating Oxidative Hair Dye Sensitization Potential Using h-CLAT
• The Japanese Ring Study of a Human Cell Line Activation Test (h-CLAT) for Predicting Skin Sensitization Potential (5^ Report) : A Study for Evaluating Preservative Skin Sensitization Potential Using h-CLAT
• A tiered approach combining the short time exposure (STE) test and the bovine corneal opacity and permeability (BCOP) assay for predicting eye irritation potential of chemicals

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