期刊
MOLECULAR MEDICINE REPORTS
卷 16, 期 5, 页码 6405-6411出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2017.7384
关键词
suppressor of cytokine signaling-1; Janus kinase 1; signal transducer and activator of transcription 1; macrophage
资金
- Science and Technology Planning Project of Guangdong Province [2012B031800291]
- Science and Technology Planning Project of Guangzhou City [201300000160]
- Tianjin Chase Sun Pharmaceutical Co., Ltd.
Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh) RNA into mouse macrophage cells, reverse transcription-quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 1 increased significantly. In addition, western blotting indicated that JAK1, STAT1 and p-STAT1 expression was significantly enhanced. Fludarabine can inhibit phosphorylation of STAT1 and SOCS1 expression. When fludarabine was added and SOCS1 shRNA was transfected, the inhibition of fludarabine was weakened, and p-STAT1 expression was upregulated. Flow cytometry detection indicated that, following the downregulation of SOCS1 expression, M1-type cells significantly increased, but the proportion of M2-type cells did not change significantly. Fludarabine can reduce the effect of SOCS1 shRNA on promoting M1-type cell polarization, and macrophages can polarize into both M1 and M2 phenotypes. Further ELISA results presented that, when downregulating SOCS1 expression, interleukin (IL)-4 and IL-10 expression was both downregulated, and tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma expression was significantly upregulated. When adding fludarabine or injecting with the traditional Chinese medicine Xuebijing, IL-4 and IL-10 expression was both significantly upregulated, and TNF-alpha and IFN-gamma expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL-4, IL-10, TNF-alpha and IFN-gamma expression presented no significant changes. The above results indicated that, when SOCS1 expression is downregulated, it will activate the JAK1/STAT1 pathway, and thereby promote the polarization of macrophages into M1 type. The findings are of great importance for understanding occurrence, development and treatment of various immune-related diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据