Division of Pharmacology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Division of Pharmacology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
J Pharmacol Sci. 2022 Jul;149(3):166-171. doi: 10.1016/j.jphs.2022.04.006. Epub 2022 May 7.
Microglia have diverse physiological and pathological functions. However, the transcriptional mechanisms remain elusive. Here we sought new transcription factors relevant to microglial functions from the microglial transcriptome of stressed mice and evaluated their roles in primary microglia. TLR2 and TLR4 agonists increased Rel, Atf3, and Cebpb and decreased Hhex in primary microglia as repeated social defeat stress. Although Hhex was not studied in microglia, TLR2 and TLR4 agonists decreased Hhex, and Hhex overexpression attenuated TLR4-increased expression of inflammation-related genes. These findings suggest that Hhex negatively regulates inflammation-related genes in microglia and that TLR2/4 activation reduces Hhex, facilitating TLR4-mediated neuroinflammation.
小胶质细胞具有多种生理和病理功能。然而，其转录机制仍不清楚。在这里，我们从小鼠应激状态下的小胶质细胞转录组中寻找与小胶质细胞功能相关的新转录因子，并评估它们在原代小胶质细胞中的作用。TLR2 和 TLR4 激动剂增加了原代小胶质细胞中的 Rel、Atf3 和 Cebpb，减少了 Hhex，如重复社交挫败应激。尽管 Hhex 尚未在小胶质细胞中研究，但 TLR2 和 TLR4 激动剂降低了 Hhex，而过表达 Hhex 则减弱了 TLR4 增加的炎症相关基因的表达。这些发现表明 Hhex 负调控小胶质细胞中的炎症相关基因，TLR2/4 激活降低了 Hhex，促进了 TLR4 介导的神经炎症。
