Immunomodulation in systemic lupus erythematosus: induction of M2 population in monocyte-derived macrophages by pioglitazone
Immunomodulation in systemic lupus erythematosus: induction of M2 population in monocyte-derived macrophages by pioglitazone
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DOI：
10.1177/0961203317701842
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发表时间：
2017-10-01
期刊：
影响因子：
2.6
通讯作者：
Memarian, A.
中科院分区：
文献类型：
--
作者：
Mohammadi, S.;Saghaeian-Jazi, M.;Memarian, A.
巨噬细胞在系统性红斑狼疮（SLE）的发病机制中的抗炎清除凋亡细胞的作用，最近得到了关注。巨噬细胞的M1/M2极化提高了巨噬细胞的能力。过氧化物酶体增殖物激活受体被认为在M2亚群的扩增中起作用。吡格列酮是一种过氧化物酶体增殖物激活受体激动剂，具有多种抗炎作用。本文研究了15例新诊断的SLE患者和10例正常人的单核细胞源性巨噬细胞在吡格列酮治疗后由SLE患者中的凋亡细胞触发的体外改变。检测巨噬细胞吞噬功能和M1/M2极化（CD 86/CD 163）。同时分析上清液中白细胞介素（IL）-10，IL-12，转化生长因子1和TNF-α的表达。在处理和未处理的单核细胞衍生的巨噬细胞中还定量IL-1和甘露糖受体C-1型的mRNA表达。我们发现SLE患者单核细胞源性巨噬细胞中的巨噬细胞增多症是有缺陷的，可能是持续炎症的主要潜在机制。吡格列酮可增强单核细胞源性巨噬细胞的交替激活，从而增强这些患者的免疫调节作用。
Macrophages have recently gained attention in systemic lupus erythematosus (SLE) pathogenesis for their role in the anti-inflammatory clearance of apoptotic cells. The M1/M2 polarization of macrophages improves efferocytic capability. Peroxisome proliferator-activated receptor is proposed to function in the expansion of the M2 subpopulation. Pioglitazone is a peroxisome proliferator-activated receptor agonist with a variety of anti-inflammatory effects. In this paper, we investigated the ex vivo alterations of monocyte-derived macrophages of 15 newly diagnosed SLE patients and 10 normal subjects triggered by apoptotic cells among SLE patients following pioglitazone treatment. The phagocytosis capacity of macrophages and M1/M2 polarization (CD86/CD163) was evaluated. The supernatants were also analyzed for the expression of interleukin (IL)-10, IL-12, transforming growth factor 1 and TNF-. The mRNA expression of IL-1 and mannose receptor C-type 1 were also quantified among treated and non-treated monocyte-derived macrophages. We found that efferocytosis is defective among monocyte-derived macrophages of SLE patients and might be a major underlying mechanism involved in the sustained inflammation. Pioglitazone could enhance alternative activation of monocyte-derived macrophages and consequently immunomodulation in these patients.