期刊
JOURNAL OF PAIN RESEARCH
卷 11, 期 -, 页码 1769-1778出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JPR.S164493
关键词
diabetes; hyperglycemia; THP-1; monocyte; TNF; inflammation
资金
- National Institutes of Health - The National Institute of General Medical Sciences (NIH/NIGMS) [R15GM109333]
Introduction: Painful diabetic neuropathy is associated with chronic inflammation, in which macrophages are the key effectors. We utilized an in vitro approach to determine the effects of high glucose on macrophage phenotype. Materials and methods: We exposed human THP-1 macrophages to normal glucose (5 mM) and a clinically relevant high glucose environment (15 mM) and measured the expression and concentration of molecules associated with a diabetic cellular phenotype. Results: We found that THP-1 macrophages in high glucose conditions did not influence the basal expression of cyclooxygenase-2, Toll-like receptor-4, or class A scavenger receptor mRNA, or the concentrations of the cytokines interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and IL-10, but induced a priming effect on tumor necrosis factor (TNF)-alpha. Then, we stimulated THP-1 macrophages with a strong pro-inflammatory stimulus lipopolysaccharide (LPS; 5 mu g/mL). After stimulation with LPS, we observed an exacerbated increase in TNF-alpha, IL-6, and MCP-1 concentration in the high glucose condition compared to the normal glucose environment. THP-1 macrophages in high glucose conditions developed tolerance to IL-10 anti-inflammatory effects (TNF-alpha production) when challenged with LPS. Conclusion: Our in vitro approach allows the study of macrophages as potential targets for therapeutic purposes since it compares them to primary human macrophages exposed to high glucose and macrophages from patients with diabetes or complications of painful diabetic neuropathy (i.e. ulcers, adipocytes, and pancreas).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据