摘要
目的分析组蛋白去乙酰化酶(HDAC)抑制剂丙戊酸(VPA)对百草枯(PQ)和脂多糖(LPS)诱导的巨噬细胞炎性极化的作用。方法小鼠巨噬细胞RAW264.7 37℃、5%CO2条件下培养,稳定传代后分组,分别给予以下处理:(1)PQ;(2)PQ+VPA(HDACⅠ和Ⅱa类抑制剂);(3)PQ+Apicidin(HDACⅠ类抑制剂);(4)PQ+MC1568(HDACⅡa类抑制剂);(5)LPS;(6)LPS+VPA;(7)LPS+Apicidin;(8)LPS+MC1568。8 h后收集各组细胞上清及细胞团,RT-PCR、ELISA及流式细胞检测巨噬细胞表型标志物的表达。结果 PQ与LPS均促进巨噬细胞向促炎表型极化;VPA、Apicidin和MC1568均抑制PQ、LPS诱导巨噬细胞表型极化作用,但抑制作用不完全相同。结论 VPA抑制PQ和LPS诱导的巨噬细胞促炎活性,但对PQ和LPS的作用方式各有特点。
Objective To analyze the effects of valproic acid （VPA）, a histone deacetylase （HDAC） inhibitor, on macrophage polarization induced by paraquat （PQ） or lipopolysaccharide （LPS）. Methods Mouse RAW264.7 cells were cultured at 37 ℃ with 5%CO2, passaged, and then given one of the following treatments： （ 1 ）PQ; （2）PQ＋VPA（classⅠ and Ⅱ a HDAC inhibitor） ; （3）PQ＋apicidin（class Ⅰ HDAC inhibitor） ; （4） PQ＋MC1568 （ class Ⅱ a HDAC inhibitor） ; （5）LPS; （ 6 ） LPS＋VPA ; （7） LPS＋apicidin ; （8） LPS＋MC1568. The ceils and culture supematants were harvested after 8 h of treatment. RT-PCR, ELISA, and flow cytometry were conducted to assess the expression levels of macmphage phenotypic markers. Results Both PQ and LPS skewed the macrophage functional polarity toward proinflammatory phenotype. VPA, apicidin, and MC1568 all inhibited PQ- and LPS-induced macmphages polarizing toward pro-inflammatory phenotype, but the inhibitory, effects were different in some ways. Conclusion VPA inhibits the proinflammatory function of macmphages induced by PQ and LPS ,but the effect of VPA on PQ- and LPS-induced macmphages has its own characteristics.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2017年第6期548-551,556,共5页
Journal of China Medical University
基金
国家自然科学基金(81372970)
关键词
百草枯
脂多糖
丙戊酸
巨噬细胞
表型转化
paraquat
lipopolysaccharide
valproic acid
macrophage
phenotypic polarization
