Blocking interleukin-1β induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes.
Blocking interleukin-1β induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes.
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作者：
Mirza RE;Fang MM;Ennis WJ;Koh TJ
糖尿病与持续性炎症和有缺陷的组织修复反应有关。本研究的假设是，白细胞介素（IL）-1β是促炎正反馈环的一部分，可维持持续的促炎伤口巨噬细胞表型，导致糖尿病愈合受损。从糖尿病人和小鼠伤口中分离的巨噬细胞表现出促炎表型，包括IL-1β的表达和分泌。糖尿病伤口环境似乎足以诱导这些炎症现象，因为体外研究表明，小鼠和人伤口的条件培养基上调促炎基因的表达，下调促愈合因子在培养的巨噬细胞中的表达。此外，使用中和抗体和来自IL-1受体敲除小鼠的巨噬细胞抑制IL-1β通路阻断了条件培养基诱导的促炎基因上调和促愈合因子下调。重要的是，使用中和抗体抑制糖尿病小鼠伤口中的IL-1β途径诱导了从促炎性到愈合相关巨噬细胞表型的转变，增加了伤口生长因子的水平，并改善了这些伤口的愈合。我们的研究结果表明，靶向IL-1β通路代表了改善糖尿病伤口愈合的新治疗方法。
Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1β 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-1β. 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-1β 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-1β 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-1β pathway represents a new therapeutic approach for improving the healing of diabetic wounds.
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影响因子：
3.8
作者：
Osborn, O.;Brownell, S. E.;Sanchez-Alavez, M.;Salomon, D.;Gram, H.;Bartfai, T.
通讯作者：
Bartfai, T.
影响因子：
--
作者：
Artlett, Carol M.;Sassi-Gaha, Sihem;Katsikis, Peter D.
通讯作者：
Katsikis, Peter D.
影响因子：
17.1
作者：
Dombrowski Y;Peric M;Koglin S;Kammerbauer C;Göss C;Anz D;Simanski M;Gläser R;Harder J;Hornung V;Gallo RL;Ruzicka T;Besch R;Schauber J
通讯作者：
Schauber J
影响因子：
4.4
作者：
Lucas, Tina;Waisman, Ari;Eming, Sabine A.
通讯作者：
Eming, Sabine A.
影响因子：
5.7
作者：
Hu, Yajing;Liang, Deyong;Peltz, Gary
通讯作者：
Peltz, Gary