Production of IL-8 in THP-1 cells following contact allergen stimulation via mitogen-activated protein kinase activation or tumor necrosis factor-alpha production.
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-alpha, IL-1beta, 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-alpha, 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-alpha 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-alpha 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.
Nukada
Yuko
Y
Kao Corporation, Safety Science Research Laboratories, Tochigi, Japan. nukada.yuko@kao.co.jp
Miyazawa
Masaaki
M
Kosaka
Nanae
N
Ito
Yuichi
Y
Sakaguchi
Hitoshi
H
Nishiyama
Naohiro
N
D000485:Allergens / Q000633:toxicity*; D002460:Cell Line; D004137:Dinitrochlorobenzene / Q000633:toxicity; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D009532:Nickel / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000485:Allergens; D004137:Dinitrochlorobenzene; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C029938:nickel sulfate; D009532:Nickel; D020928:Mitogen-Activated Protein Kinases