Glutaredoxin 1 regulates macrophage polarization through mediating glutathionylation of STAT1
Autor: | Qingrong Liu, Shanze Chen, Xiaoying Wang, Tongzhou Cai, Junyue Pan, Yi Wang, Jingyu Li, Junli Chen, Hongyu Ren, Yuhao Li, Ning Huang, Yuhan Luo, Ruofan Liu, Lijuan Guo |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Chemokine Immunoprecipitation macrophage polarization Glutaredoxin Macrophage polarization lcsh:RC254-282 Mice 03 medical and health sciences 0302 clinical medicine STAT1 Western blot medicine Animals Transcription factor Glutaredoxins medicine.diagnostic_test biology business.industry Macrophages Cell Polarity Original Articles General Medicine lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology Mice Inbred C57BL RAW 264.7 Cells STAT1 Transcription Factor 030104 developmental biology Oncology 030220 oncology & carcinogenesis STAT protein biology.protein Original Article business glutathionylation |
Zdroj: | Thoracic Cancer, Vol 11, Iss 10, Pp 2966-2974 (2020) Thoracic Cancer |
ISSN: | 1759-7706 1759-7714 |
Popis: | Background Macrophage polarization affects tumor growth, metabolism, and many other tumor processes. M1 macrophages can promote antitumor immunity response. Signal transducer and activator of transcription 1 (STAT1) is one of the critical transcription factors in this process, which promotes the expression of a series of inflammatory molecules. STAT1 has been reported as a potential target of reactive oxygen species (ROS)‐induced glutathionylation, while the glutathionylation of STAT1 in macrophages and its underlying regulatory mechanism remains unclear. Glutaredoxin 1 (Grx1) functions as a deglutathionylation enzyme, which regulates the activities of many proteins through reversing glutathionylation. Methods GeneChip and RT‐qPCR was first applied to test the mRNA level of Grx1 in M1 macrophages. Western blot was then used to evaluate the variations of the Grx1 protein expression in M1 macrophages. Next, immunoprecipitation was used to investigate the glutathionylated STAT1 in both wild‐type and Grx1−/− mouse macrophages. Finally, the induced alterations of STAT1 activity and function by Grx1 in M1 macrophage were examined by western blot and RT‐qPCR. Results In M1‐type macrophages, the levels of Grx1 were elevated. Glutathionylation of STAT1 was negatively regulated by Grx1. Furthermore, depletion of Grx1 increased the activity of STAT1, and thereby promoted the mRNA level of C‐X‐C motif chemokine ligand 9 (CXCL9) during M1‐type polarization of macrophages. Conclusions Grx1 controlled deglutathionylation of STAT1, which in turn might regulate M1‐type polarization of macrophages. In M1‐type macrophages, the levels of Grx1 were elevated. Glutathionylation of STAT1 was negatively regulated by Grx1. Furthermore, depletion of Grx1 increased the activity of STAT1, and promoted the mRNA levels of CXCL9 in the process of macrophages polarized to M1 phenotype. |
Databáze: | OpenAIRE |
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