Macrophages play an important role in aldosterone-induced myocardial fibrosis, in which the first key steps are macrophage recruitment and infiltration. We hypothesized that IL-6 may be a key mediator of aldosterone-induced macrophage recruitment and infiltration. To test this hypothesis, we designed cell studies with a human monocytic cell line THP-1 that with monocyte/macrophage functions to explore the signaling pathway of aldosterone-induced macrophage infiltration, and further investigated the phenomenon and consequent pathway in aldosterone-infused mice studies. The results showed that aldosterone induced the expression of IL-6 via mineralocorticoid receptors, and enhanced THP-1 cell migration and infiltration. Further experiments using a protease array and siRNA revealed that expressions of MMP-1 and MMP-9 were associated with aldosterone-induced macrophage infiltration. In addition, aldosterone-induced MMP-1 and MMP-9 expressions were mediated via cyclooxygenase-II and prostaglandin E2/EP-2 and EP-4 receptors. In aldosterone-infused mice, mRNA expressions of MMP-1, MMP-9 and COX-2 in peripheral blood monocytic cells were significantly increased. Moreover, the number of mouse macrophage-restricted F4/80 protein-positive cells in the myocardium was significantly higher in the aldosterone-infused mice compared with control mice. The increase in F4/80-positive cells in the myocardium was suppressed in the aldosterone-infused mice with the aldosterone antagonist eplerenone or anti-IL-6 antibody treatment. In conclusion, interleukin-6 played an important role in aldosterone-induced macrophage recruitment and infiltration in the myocardium.

中文翻译：

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白细胞介素6在醛固酮诱导的心肌巨噬细胞募集和浸润中起关键作用。

巨噬细胞在醛固酮诱导的心肌纤维化中起重要作用，其中首要的关键步骤是募集和浸润巨噬细胞。我们假设IL-6可能是醛固酮诱导的巨噬细胞募集和浸润的关键介质。为了验证该假设，我们设计了具有单核细胞/巨噬细胞功能的人类单核细胞系THP-1的细胞研究，以探索醛固酮诱导的巨噬细胞浸润的信号传导途径，并进一步研究了醛固酮灌注小鼠研究中的现象和随后的途径。结果表明，醛固酮通过盐皮质激素受体诱导IL-6的表达，并增强THP-1细胞的迁移和浸润。使用蛋白酶阵列和siRNA进行的进一步实验表明MMP-1和MMP-9的表达与醛固酮诱导的巨噬细胞浸润有关。此外，醛固酮诱导的MMP-1和MMP-9表达是通过环氧合酶II和前列腺素E2 / EP-2和EP-4受体介导的。在注射醛固酮的小鼠中，外周血单核细胞中MMP-1，MMP-9和COX-2的mRNA表达显着增加。此外，与对照小鼠相比，醛固酮灌注小鼠的心肌中小鼠巨噬细胞限制性F4 / 80蛋白阳性细胞的数量明显更高。在用醛固酮拮抗剂依普利农或抗IL-6抗体治疗的输注了醛固酮的小鼠中，心肌中F4 / 80阳性细胞的增加被抑制。综上所述，