Production of IL-8 in THP-1 cells following contact allergen stimulation via mitogen-activated protein kinase activation or tumor necrosis factor-α production
スポンサーリンク
概要
- 論文の詳細を見る
Contact allergens induce in vitro and in vivo the activation of dendritic cells (DC) and Langerhans cells (LC), which includes the up-regulation of surface marker expression (e.g. CD86, CD54) and cytokine production (e.g. TNF-α, IL-1β, IL-8). The mitogen-activated protein kinase (MAPK) pathway also has a crucial role in this activation. However, the extent of MAPK involvement in the IL-8 production during DC/LC activation is not well understood. Earlier, we reported that contact allergens activated THP-1 cells, human monocytic cell line, like LC/DC in vitro. In this study, we further characterize the mechanism of IL-8 production using THP-1 cells as surrogate DCs. First, we evaluated the potential of 23 chemicals with different skin sensitization potencies to predominantly induce IL-8 production in vitro. Next we investigated the role of MAPK signaling and TNF-α, which is known to have autocrine effects on DC activation (e.g., IL-8 production). Inhibition of extracellular signal-regulated kinase (ERK), one of the MAPK pathways, suppressed the IL-8 production induced by both 2,4-dinitrochlorobenzene (DNCB) and nickel sulfate (NiSO_4), and inhibition of p38 MAPK, a second MAPK pathway, significantly suppressed IL-8 production induced by only DNCB. Additionally, neutralization of TNF-α activity suppressed IL-8 production in THP-1 cells exposed to DNCB and NiSO_4. In conclusion, IL-8 production was predominantly induced in THP-1 cells following allergen stimulation, and MAPK pathways and TNF-α were involved in the IL-8 production induced by DNCB and NiSO_4. A better understanding of the mechanism of DC activation in vitro might lead to the clarification of the in vivo skin sensitization mechanism.
- 日本トキシコロジー学会の論文
- 2008-05-01
著者
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Sakaguchi Hitoshi
Safety Science Research Laboratories, Kao Corporation
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Miyazawa Masaaki
Kao Corporation Safety Science Research Laboratories
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Nukada Yuko
Kao Corporation, Safety Science Research Laboratories
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Kosaka Nanae
Kao Corporation, Safety Science Research Laboratories
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Ito Yuichi
Kao Corporation, Safety Science Research Laboratories
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Sakaguchi Hitoshi
Kao Corporation, Safety Science Research Laboratories
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Nishiyama Naohiro
Kao Corporation, Safety Science Research Laboratories
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Nishiyama Naohiro
Kao Corporation
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Sakaguchi Hitoshi
Kao Corporation
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Nukada Yuko
Kao Corporation
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Ito Yuichi
Kao Corporation
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Kosaka Nanae
Kao Corporation
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Suzuki Hiroyuki
Kao Corporation Product Quality Management Division
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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
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