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.
Kao Corporation, Safety Science Research Laboratories, Tochigi, Japan. nukada.yuko@kao.co.jp
Yuko
Y
Nukada
Masaaki
M
Miyazawa
Nanae
N
Kosaka
Yuichi
Y
Ito
Hitoshi
H
Sakaguchi
Naohiro
N
Nishiyama
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