Role of MAPK signaling pathway in the activation of dendritic type cell line, THP-1, induced by DNCB and NiSO_4

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概要

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• The activation of dendritic cells (DC), including Langerhans cells (LC) that reside within the epidermis, is a critical event in the induction phase of allergic contact hypersensitivity. Although recently, p38 mitogen-activated protein kinase (MAPK) has been reported to play a role in the activation of DC induced by allergens, the signaling pathways involved in this process have yet to be determined. We previously found that THP-1 cells have a high capacity to induce TNF-α release and CD86, CD54, and CD40 expression following allergen treatment; reflecting in vitro allergen-induced DC activation during skin sensitization. In this study, we investigated the signaling pathways in THP-1 cells activated by two representative allergens, DNCB and NiSO_4. We found that DNCB and NiSO_4 induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK activation selectively blocked DNCB-induced TNF-α release, but not NiSO_4-induced release. In contrast, inhibition of ERK pathways selectively suppressed NiSO_4-induced TNF-α release but not DNCB-induced release. In addition, we found that the inhibition of p38 MAPK and ERK pathways caused a selective inhibition of CD86, CD54, and/or CD40 expression following treatment with DNCB or NiSO_4. In particular, inhibition of p38 MAPK suppressed CD86, CD54, and CD40 expression induced by DNCB and CD86 expression induced by NiSO_4 while inhibition of ERK pathways suppressed CD86, CD54 and CD40 expression induced by DNCB and NiSO_4. These data indicate that both DNCB and NiSO_4 activate p38 MAPK and ERK, and thereby stimulate TNF-α release and phenotypic changes through the different signal transduction pathways.

• 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
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