Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages

Xuan Dongying; Han Qianqian; Tu QishengZhang LanYu LimingMurry DanaTu TianchiTang YinLian Jane B.Stein Gary S.Valverde PalomaZhang JincaiChen Jake

摘要

Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in peritoneal macrophages isolated from DIO mice when challenged with Porphyromonas gingivalis LPS (pg.lps). To elucidate the interaction of APN and JMJD3 involved in macrophage transformation in the context of inflammation, we designed the loss and gain-function experiments of APN in vivo with APN(-/-) mice with experimental periodontitis and in vitro with macrophage isolated from APN(-/-) mice. For the first time, we found that APN can help to reduce periodontitis-related bone loss, modulate JMJD3 and IRF4 expression, and macrophage infiltration. Therefore, it can be inferred that APN may contribute to anti-inflammation macrophage polarization by regulating JMJD3 expression, which provides a basis for macrophage-centered epigenetic therapeutic strategies. J. Cell. Physiol. 231: 1090-1096, 2016. (c) 2015 Wiley Periodicals, Inc.

机译：新兴证据表明一个重要的角色表观遗传机制在调制信号在巨噬细胞极化和炎症。组蛋白demethylase JMJD3, JmjC家庭M2所需极化也是必需的为有效感应多个M1基因脂多糖(LPS)。JMJD3炎症在肥胖的上下文仍然是未知的。首先检查JMJD3的表达巨噬细胞与骨髓和脂肪组织饮食诱导的肥胖小鼠(戴奥)。结果表明,JMJD3衰减在肥胖。通过抑制在脂肪组织肥胖、巨噬细胞功能开关从M1, M2极化,从而衰减慢性炎症。表明APN JMJD3老年病,减少巨噬细胞浸润肥胖的脂肪组织,并废除了老年病的JMJD3腹膜巨噬细胞与戴奥老鼠当挑战Porphyromonas gingivalis有限合伙人(pg.lps)。阐明比例导引和JMJD3之间的交互在巨噬细胞转变炎症的背景下,我们设计了损失和增益函数的导引和体内实验APN(- / -)小鼠实验性牙周炎与巨噬细胞体外分离比例导引(- / -)老鼠。有助于减少periodontitis-related骨质流失,调节JMJD3 IRF4的表情,巨噬细胞浸润。APN可能导致的推断抗炎巨噬细胞极化的调节JMJD3表达式,提供了一个依据macrophage-centered表观遗传治疗策略。1090 - 1096年,2016年。

Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages

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