NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland.
Pharmacol Rep. 2022 Oct;74(5):909-919. doi: 10.1007/s43440-022-00384-x. Epub 2022 Jul 7.
Microglia play a major role in the development of brain inflammation after central nervous system injury. On the other hand, microglia also participate in the repair process. The dualistic role of these cells results from the fact that various states of their activation are associated with specific phenotypes. The M1 phenotype is responsible for the production of proinflammatory mediators, whereas the M2 microglia release anti-inflammatory and trophic factors and take part in immunosuppressive and neuroprotective processes. The histone deacetylase inhibitor sodium butyrate (SB) shows anti-inflammatory and neuroprotective effects in some animal models of brain injury. The aim of this study was to examine the effects of sodium butyrate on the proliferation and M1/M2 polarization of primary microglial cells after oxygen and glucose deprivation (OGD) in vitro.
Primary microglial cultures were prepared from 1-day-old rats, subjected to the OGD procedure and treated with SB (0.1 mM, 1 mM and 10 mM). The effect of OGD and SB on microglial proliferation was assessed by double immunofluorescence, and microglial phenotypes were evaluated by qPCR.
The OGD procedure stimulated the proliferation of microglia after 24 h of culturing, and SB treatment reduced the division of these cells. This effect was inversely proportional to the SB concentration. The OGD procedure increased proinflammatory CD86 and IL1β gene expression and reduced the expression of the anti-inflammatory M2 markers arginase and CD200 in microglia.
SB can change the polarization of microglia after OGD from an unfavourable M1 to a beneficial M2 phenotype. Our results show that SB is a potential immunosuppressive agent that can modulate microglial activation stimulated by ischaemic-like conditions.
小胶质细胞在中枢神经系统损伤后大脑炎症的发展中起主要作用。另一方面，小胶质细胞也参与修复过程。这些细胞的双重作用是由于其激活的各种状态与特定表型相关。M1 表型负责产生促炎介质，而 M2 小胶质细胞释放抗炎和营养因子，并参与免疫抑制和神经保护过程。组蛋白去乙酰化酶抑制剂丁酸钠（SB）在一些脑损伤动物模型中表现出抗炎和神经保护作用。本研究旨在研究丁酸钠对体外氧葡萄糖剥夺（OGD）后原代小胶质细胞增殖和 M1/M2 极化的影响。
从小鼠 1 日龄制备原代小胶质细胞培养物，进行 OGD 处理，并给予 SB（0.1 mM、1 mM 和 10 mM）处理。通过双免疫荧光评估 OGD 和 SB 对小胶质细胞增殖的影响，通过 qPCR 评估小胶质细胞表型。
OGD 处理后 24 小时培养物中小胶质细胞增殖受到刺激，SB 处理减少了这些细胞的分裂。这种作用与 SB 浓度呈反比。OGD 处理增加了促炎 CD86 和 IL1β 基因表达，降低了小胶质细胞中抗炎 M2 标志物精氨酸酶和 CD200 的表达。
SB 可使 OGD 后小胶质细胞的极化从不利的 M1 向有利的 M2 表型转变。我们的结果表明，SB 是一种潜在的免疫抑制剂，可调节类似缺血条件刺激的小胶质细胞激活。
