Regulation of inflammatory gene expression in macrophages by epithelial-stromal interaction 1 (Epsti1)
Regulation of inflammatory gene expression in macrophages by epithelial-stromal interaction 1 (Epsti1)
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DOI：
10.1016/j.bbrc.2017.12.014
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发表时间：
2018-02-05
影响因子：
3.1
通讯作者：
Hahn, Myong-Joon
中科院分区：
文献类型：
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作者：
Kim, Young-Hoon;Lee, Jae-Rin;Hahn, Myong-Joon
上皮-基质相互作用 1 (EPSTI1) 最初是作为乳腺癌上皮细胞中共培养的基质成纤维细胞诱导的基因被发现的。关于 Epsti1 在癌症恶性肿瘤中的作用有许多报道。 Epsti1 现在在调节癌症方面众所周知。最近，Epsti1在免疫反应中的作用被报道；这些报告表明 Epsti1 在免疫功能、免疫特权和自身免疫性疾病中的作用。此外，他们表明 Epsti1 在各种类型的免疫细胞中表达。在这项研究中，我们观察到 Epsti1 在暴露于 IFN γ 和脂多糖 (LPS) 的巨噬细胞中高度表达，这通常会激活巨噬细胞。巨噬细胞极化为经典激活 (M1) 或替代激活 (M2) 对于增强针对各种感染的反应非常重要。 M1 和 M2 类型的巨噬细胞在免疫系统中具有独特的作用。然而，巨噬细胞类型调节的分子机制尚未明确。我们的结果表明，Epsti1 缺陷的骨髓源性巨噬细胞 (BMDM) 中 M2 型巨噬细胞表型增强。此外，Epsti1 缺陷通过抑制 Stat1 和 p65 核定位和磷酸化来抑制 BMDM 中促炎基因的诱导。令人惊讶的是，Epsti1-/- 小鼠腹膜腔中 M1 巨噬细胞数量减少。这些发现确定 Epsti1 通过 Stat1 和 p65 途径调节巨噬细胞活化和极化，并表明 Epsti1 在针对炎症性疾病的免疫疗法中具有潜在的重要作用。 (C) 2018 Elsevier Inc. 保留所有权利。
Epithelial-stromal interaction 1 (EPSTI1) was first discovered as a gene induced in breast cancer epithelial cells by co-cultured stromal fibroblasts. There are many reports on the role of Epsti1 in cancer malignancy. Epsti1 is now well known in regulating cancer. Recently, the role of Epsti1 in the immune response has been reported; these reports suggest the role of Epsti1 in immune function, immune privilege, and autoimmune diseases. Furthermore, they show that Epsti1 is expressed in various types of immune cells. In this study, we observed that Epsti1 is highly expressed in macrophages exposed to IFN gamma and lipopolysaccharide (LPS), which classically activates macrophages. Polarization of macrophage to classically activated (M1) or alternatively activated (M2) is important for mounting responses against various infections. The M1 and M2 types of macrophage have a distinct role in the immune system. However, the molecular mechanism of modulation of the macrophage type is not well defined. Our results showed that the M2 type macrophage phenotype is enhanced in Epsti1-deficient bone marrow-derived macrophages (BMDM). In addition, Epsti1 deficiency suppresses induction of pro-inflammatory genes in BMDMs via inhibition of Stat1 and p65 nuclear localization and phosphorylation. Surprisingly, Epsti1-/- mice show decreased numbers of M1 macrophages in the peritoneal cavity. These findings identify Epsti1 as a modulator of macrophage activation and polarization via the Stat1 and p65 pathways, and suggest a potentially important role of Epsti1 in immunotherapies against inflammatory diseases. (C) 2018 Elsevier Inc. All rights reserved.