Department of Paediatrics, First Subsidiary Hospital, University of Science and Technology of He'nan, 471000, China.
Department of Paediatrics, First Subsidiary Hospital, University of Science and Technology of He'nan, 471000, China.
Life Sci. 2019 Mar 15;221:13-19. doi: 10.1016/j.lfs.2019.02.004. Epub 2019 Feb 6.
Excessive inflammation is fundamental in the pathophysiology of Mycoplasma pneumoniae (MP)-induced respiratory infection in children. Histone deacetylase 5 (HDAC5) is involved in the regulation of inflammation, however, whether it associates with immunity against MP infection is not determined. We report here that HDAC5 expression is decreased in peripheral blood mononuclear cells (PBMCs) from Mycoplasma pneumoniae pneumonia (MPP) children as well as in MP-infected peritoneal and THP-1 macrophages. Functionally, HDAC5 overexpression promotes and its depletion inhibits MP-induced proinflammatory cytokine production in THP-1 macrophages. Mechanistically, HDAC5 modulates NF-κB activation in MP-infected THP-1 macrophages, and moreover, inhibition of NF-κB activity via pharmacological inhibitor Bay 11-7082 attenuates the promotive effect of HDAC5 on MP-induced proinflammatory cytokine production in THP-1 macrophages, hence suggesting that HDAC5 promotes MP-induced inflammatory response in macrophages through NF-κB activation. Together, this study reveals a novel function of HDAC5 in promoting MP-induced inflammation and implies the possible clinical significance in controlling inflammation that underlies MMP pathophysiology.
过度炎症反应是儿童肺炎支原体（MP）感染病理生理学的基础。组蛋白去乙酰化酶 5（HDAC5）参与炎症的调节，但它是否与针对 MP 感染的免疫有关尚不确定。我们在此报告，HDAC5 的表达在肺炎支原体肺炎（MPP）患儿的外周血单核细胞（PBMC）以及 MP 感染的腹膜和 THP-1 巨噬细胞中降低。功能上，HDAC5 的过表达促进，其耗竭抑制 MP 诱导的 THP-1 巨噬细胞中促炎细胞因子的产生。在机制上，HDAC5 调节 MP 感染的 THP-1 巨噬细胞中 NF-κB 的激活，此外，通过药理学抑制剂 Bay 11-7082 抑制 NF-κB 活性，减弱了 HDAC5 对 THP-1 巨噬细胞中 MP 诱导的促炎细胞因子产生的促进作用，这表明 HDAC5 通过 NF-κB 激活促进巨噬细胞中 MP 诱导的炎症反应。综上所述，本研究揭示了 HDAC5 在促进 MP 诱导的炎症反应中的新功能，并暗示了在控制 MMP 病理生理学基础上的炎症方面可能具有临床意义。
