(a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France.
(a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France; Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, Hubei Province, China.
Exp Cell Res. 2015 Feb 1;331(1):152-163. doi: 10.1016/j.yexcr.2014.11.004. Epub 2014 Nov 15.
Aldosterone and mineralocorticoid receptors are important regulators of inflammation. During this process, chemokines and extracellular matrix degradation by matrix metalloproteases, such as MMP-9, help leukocytes reaching swiftly and infiltrating the injured tissue, two processes essential for tissue repair. Leukocytes, such as neutrophils, are a rich source of MMP-9 and possess mineralocorticoid receptors (MR). The aim of our study was to investigate whether aldosterone was able to regulate proMMP-9, active MMP-9 and MMP-9/NGAL production in human neutrophils. Here we show that aldosterone increased MMP-9 mRNA in a dose- and time-dependent manner. This hormone up-regulated also dose-dependently proMMP-9 and active MMP-9 protein release as well as the MMP-9/NGAL protein complex. PI3K, p38 and ERK1/2 inhibition diminished these aldosterone-induced neutrophil productions. Furthermore, spironolactone, a MR antagonist, counteracted aldosterone-induced increases of proMMP-9, active MMP-9 and MMP-9/NGAL complex. These findings indicate that aldosterone could participate in tissue repair by modulating neutrophil activity and favoring extracellular matrix degradation.
醛固酮和盐皮质激素受体是炎症的重要调节因子。在这个过程中，趋化因子和细胞外基质的降解，如基质金属蛋白酶 MMP-9，可以帮助白细胞迅速到达并浸润受损组织，这两个过程对组织修复至关重要。白细胞，如中性粒细胞，是 MMP-9 的丰富来源，并具有盐皮质激素受体 (MR)。我们的研究目的是研究醛固酮是否能够调节人中性粒细胞中的 proMMP-9、活性 MMP-9 和 MMP-9/NGAL 的产生。在这里，我们表明醛固酮以剂量和时间依赖的方式增加 MMP-9 mRNA。这种激素还以剂量依赖的方式上调 proMMP-9 和活性 MMP-9 蛋白释放以及 MMP-9/NGAL 蛋白复合物。PI3K、p38 和 ERK1/2 的抑制作用减弱了这些醛固酮诱导的中性粒细胞产生。此外，MR 拮抗剂螺内酯拮抗了醛固酮诱导的 proMMP-9、活性 MMP-9 和 MMP-9/NGAL 复合物的增加。这些发现表明，醛固酮可以通过调节中性粒细胞的活性和促进细胞外基质的降解来参与组织修复。
