Son Yonghae, Kim Bo-Young, Park Young Chul, Eo Seong-Kug, Cho Hyok-Rae, Kim Koanhoi
Department of Pharmacology, Pusan National University School of Medicine, Yangsan 50612, Korea.
Institute of Marine BioTechnology, Pusan National University, Busan 46241, Korea.
Korean J Physiol Pharmacol. 2017 May;21(3):301-308. doi: 10.4196/kjpp.2017.21.3.301. Epub 2017 Apr 21.
27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determine roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors. Treatment with LY294002 or U0126 resulted in recovery of endocytic activity which was reduced by 27OHChol. CD197 expression and cell adherence enhanced by 27OHChol were attenuated in the presence of the inhibitors. Transcription and surface expression of CD molecules involved in atherosclerosis such as CD105, CD137 and CD166 were also significantly decreased by treatment with LY294002 and U0126. These results mean that the PI3K and the ERK signaling pathways are necessary for differentiation of monocytic cells into mDCs and involved in over-expression of atherosclerosis-associated molecules in response to 27OHChol.
27-羟基胆固醇可诱导单核细胞分化为成熟树突状细胞，即mDCs。在本研究中，我们试图确定PI3K和ERK信号通路在27-羟基胆固醇诱导的分化过程中的作用。在用PI3K抑制剂LY294002和ERK抑制剂U0126处理的情况下，27-羟基胆固醇刺激诱导的mDC特异性标志物如CD80、CD83和CD88的上调显著降低。在存在抑制剂的情况下，27-羟基胆固醇升高的MHC I类和II类分子的表面表达降至基础水平。用LY294002或U0126处理可使被27-羟基胆固醇降低的内吞活性恢复。在存在抑制剂的情况下，27-羟基胆固醇增强的CD197表达和细胞黏附作用减弱。用LY294002和U0126处理也可显著降低参与动脉粥样硬化的CD分子如CD105、CD137和CD166的转录和表面表达。这些结果表明，PI3K和ERK信号通路对于单核细胞分化为mDCs是必需的，并且参与了对27-羟基胆固醇应答时动脉粥样硬化相关分子的过表达。
