期刊
DIABETES
卷 62, 期 7, 页码 2579-2587出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-1450
关键词
-
资金
- National Institutes of Health [R01GM092850]
Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1 beta is part of a proinflammatory positive feedback loop that sustains a persistent proinflammatory wound macrophage phenotype that contributes to impaired healing in diabetes. Macrophages isolated from wounds in diabetic humans and mice exhibited a proinflammatory phenotype, including expression and secretion of IL-1 beta. The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena because in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of proinflammatory genes and downregulates expression of prohealing factors in cultured macrophages. Furthermore, inhibiting the IL-1 beta pathway using a neutralizing antibody and macrophages from IL-1 receptor knockout mice blocked the conditioned medium-induced upregulation of proinflammatory genes and downregulation of prohealing factors. Importantly, inhibiting the IL-1 beta pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from proinflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors, and improved healing of these wounds. Our findings indicate that targeting the IL-1 beta pathway represents a new therapeutic approach for improving the healing of diabetic wounds.
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