Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type

Liang,Yan‑Bing; Tang,Hao; Chen,Zhi‑Bin; Zeng,Li‑Jin; Wu,Jing‑Guo; Yang,Wen; Li ,Zhen‑Yu; Ma,Zhong‑Fu

doi:10.3892/mmr.2017.7384

Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type

Authors:
- Yan‑Bing Liang
- Hao Tang
- Zhi‑Bin Chen
- Li‑Jin Zeng
- Jing‑Guo Wu
- Wen Yang
- Zhen‑Yu Li
- Zhong‑Fu Ma
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Affiliations: Department of General Internal Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: August 29, 2017 https://doi.org/10.3892/mmr.2017.7384
Pages: 6405-6411

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Abstract

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)‑α and interferon (IFN)‑γ 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‑α and IFN‑γ expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL‑4, IL‑10, TNF‑α and IFN‑γ 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.

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