Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages
Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages
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DOI：
10.1161/01.cir.0000127953.98131.ed
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发表时间：
2004-05-04
期刊：
影响因子：
37.8
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Kumada, M;Kihara, S;Matsuzawa, Y
背景-血管炎症和随后的基质降解在动脉粥样硬化的发展中起重要作用.我们以前报道过脂联素，一种脂肪特异性的血浆蛋白，在损伤的动脉中积累并减弱血管炎症反应。临床上，慢性肾功能衰竭患者高血浆脂联素水平与低心血管事件发生率相关。本研究旨在阐明脂联素对基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）在人单核细胞衍生的macrophages.Methods和Results -人单核细胞衍生的巨噬细胞与生理浓度的人重组脂联素孵育指定的时间的影响。脂联素处理剂量依赖性地增加TIMP-1 mRNA水平，而不影响MMP-9 mRNA水平。脂联素也增加TIMP-1分泌到媒体，而MMP-9的分泌和活性不变。时程实验表明，TIMP-1 mRNA水平在脂联素处理24小时开始增加，并在48小时显著升高。脂联素在6 h内显著增加白细胞介素-10（IL-10）mRNA在转录水平的表达，并在24 h内显著增加IL-10蛋白的分泌。抗IL-10单克隆抗体与脂联素共处理完全废除脂联素诱导的TIMP-1 mRNA expression.Conclusions -脂联素通过IL-10诱导选择性地增加TIMP-1在人单核细胞源性巨噬细胞中的表达。这项研究首次确定了脂联素/IL-10对血管炎症的相互作用。
Background - Vascular inflammation and subsequent matrix degradation play an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipose-specific plasma protein, accumulated to the injured artery and attenuated vascular inflammatory response. Clinically, high plasma adiponectin level was associated with low cardiovascular event rate in patients with chronic renal failure. The present study was designed to elucidate the effects of adiponectin on matrix metalloproteinases ( MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in human monocyte-derived macrophages.Methods and Results - Human monocyte-derived macrophages were incubated with the physiological concentrations of human recombinant adiponectin for the time indicated. Adiponectin treatment dose-dependently increased TIMP-1 mRNA levels without affecting MMP-9 mRNA levels. Adiponectin also augmented TIMP-1 secretion into the media, whereas MMP-9 secretion and activity were unchanged. Time course experiments indicated that TIMP-1 mRNA levels started to increase at 24 hours of adiponectin treatment and were significantly elevated at 48 hours. Adiponectin significantly increased interleukin-10 (IL-10) mRNA expression at the transcriptional level within 6 hours and significantly increased IL-10 protein secretion within 24 hours. Cotreatment of adiponectin with anti-IL-10 monoclonal antibody completely abolished adiponectin-induced TIMP-1 mRNA expression.Conclusions - Adiponectin selectively increased TIMP-1 expression in human monocyte-derived macrophages through IL-10 induction. This study identified, for the first time, the adiponectin/IL-10 interaction against vascular inflammation.