High glucose increases the expression of proinflammatory cytokines and secretion of TNF伪 and 尾-hexosaminidase in human mast cells

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• 作者：Kanji Nagai^a ; ^b ; Tatsunobu Fukushima^b ; Hideaki Oike^a ; Masuko Kobori^a ; ^{kobori@affrc.go.jp}
• 关键词：High glucose ; Mast cell ; Reactive oxygen species ; Proinflammatory cytokine ; 尾-hexosaminidase
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 July, 2012
• 卷：687
• 期：1-3
• 页码：39-45
• 文件大小：955 K

摘要

Epidemiological studies demonstrated that obesity, which is a high-risk factor for development of hyperglycemia-associated metabolic syndromes, is associated with prevalence/incidence of allergic diseases. To elucidate the underlying mechanisms of the relationship between hyperglycemia and allergy, we examined the effect of high glucose on the activation of human mast cell lines, HMC-1 and LAD2. HMC-1 and LAD2 cells were cultured in low (5.5 mM) and high (25 mM)-glucose Dulbecco's modified Eagle's medium (DMEM). High鈥恎lucose medium increased the intracellular reactive oxygen species levels in HMC-1 and LAD2 cells after 2 days of incubation; in HMC-1 cells, the expression levels of tumor necrosis factor (TNF) 伪, interleukin (IL)-1尾, IL-6, and IL-13 were increased significantly. The 尾-hexosaminidase release rates were not significantly different between LAD2 cells cultured in both media; however, the intracellular and extracellular activities of 尾-hexosaminidase in cells were significantly higher in high-glucose than in low-glucose media. High glucose increased the secretion of TNF伪 by unstimulated HMC-1 cells and IgE crosslinking-stimulated LAD2 cells. High glucose increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs), which regulate the expression of TNF伪 and other inflammatory cytokines, in both HMC-1 and LAD2 cells. Thus, high glucose increased the expression of proinflammatory and proallergic cytokines, the secretion of TNF伪, and 尾-hexosaminidase activity in human mast cells. Our result suggests that hyperglycemia promotes the activation of human mast cells associated with allergy and inflammation under unstimulated and stimulated conditions.