Tsc1 is a Critical Regulator of Macrophage Survival and Function
Background/Aims: Tuberous sclerosis complex 1 (Tsc1) has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagoc...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/430306 |
| _version_ | 1818309525621440512 |
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| author | Chunmin Fang Juan Yu Yuechen Luo Song Chen Weiqiang Wang Chunxiao Zhao Zhina Sun Wantong Wu Wei Guo Zhongchao Han Xiao Hu Fang Liao Xiaoming Feng |
| author_facet | Chunmin Fang Juan Yu Yuechen Luo Song Chen Weiqiang Wang Chunxiao Zhao Zhina Sun Wantong Wu Wei Guo Zhongchao Han Xiao Hu Fang Liao Xiaoming Feng |
| author_sort | Chunmin Fang |
| collection | DOAJ |
| description | Background/Aims: Tuberous sclerosis complex 1 (Tsc1) has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagocytosis of macrophages. Methods: Mice with Tsc1 homozygous deletion in myeloid cells (LysMCreTsc1flox/flox; Tsc1 KO) were obtained by crossing Tsc1flox/flox mice with mice expressing Cre recombinase under the control of Lysozyme promoter (LysMCre). The apoptosis and growth of macrophages were determined by flow cytometry and Real-time PCR (RT-PCR). The phagocytosis was determined using a Vybrant™ phagocytosis assay kit. The migration of macrophages was determined using transwell migration assay. Results: Peritoneal macrophages of Tsc1 KO mice exhibited increased apoptosis and enlarged cell size. Both M1 and M2 phenotypes in Tsc1-deficient macrophages were elevated in steady-state as well as in inflammatory conditions. Tsc1-deficient macrophages demonstrated impaired migration and reduced expression of chemokine receptors including CCR2 and CCR5. Phagocytosis activity and ROS production were enhanced in Tsc1-deficient macrophages. Furthermore, pharmacological inhibition of the mammalian target of rapamycin complex 1 (mTORC1) partially reversed the aberrance of Tsc1-deficient macrophages. Conclusion: Tsc1 plays a critical role in regulating macrophage survival, function and polarization via inhibition of mTORC1 activity. |
| first_indexed | 2024-12-13T07:31:33Z |
| format | Article |
| id | doaj.art-5bbe621e45a940089b344bca155b90e2 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T07:31:33Z |
| publishDate | 2015-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-5bbe621e45a940089b344bca155b90e22022-12-21T23:55:12ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013641406141810.1159/000430306430306Tsc1 is a Critical Regulator of Macrophage Survival and FunctionChunmin FangJuan YuYuechen LuoSong ChenWeiqiang WangChunxiao ZhaoZhina SunWantong WuWei GuoZhongchao HanXiao HuFang LiaoXiaoming FengBackground/Aims: Tuberous sclerosis complex 1 (Tsc1) has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagocytosis of macrophages. Methods: Mice with Tsc1 homozygous deletion in myeloid cells (LysMCreTsc1flox/flox; Tsc1 KO) were obtained by crossing Tsc1flox/flox mice with mice expressing Cre recombinase under the control of Lysozyme promoter (LysMCre). The apoptosis and growth of macrophages were determined by flow cytometry and Real-time PCR (RT-PCR). The phagocytosis was determined using a Vybrant™ phagocytosis assay kit. The migration of macrophages was determined using transwell migration assay. Results: Peritoneal macrophages of Tsc1 KO mice exhibited increased apoptosis and enlarged cell size. Both M1 and M2 phenotypes in Tsc1-deficient macrophages were elevated in steady-state as well as in inflammatory conditions. Tsc1-deficient macrophages demonstrated impaired migration and reduced expression of chemokine receptors including CCR2 and CCR5. Phagocytosis activity and ROS production were enhanced in Tsc1-deficient macrophages. Furthermore, pharmacological inhibition of the mammalian target of rapamycin complex 1 (mTORC1) partially reversed the aberrance of Tsc1-deficient macrophages. Conclusion: Tsc1 plays a critical role in regulating macrophage survival, function and polarization via inhibition of mTORC1 activity.http://www.karger.com/Article/FullText/430306MacrophagemTORTsc1 |
| spellingShingle | Chunmin Fang Juan Yu Yuechen Luo Song Chen Weiqiang Wang Chunxiao Zhao Zhina Sun Wantong Wu Wei Guo Zhongchao Han Xiao Hu Fang Liao Xiaoming Feng Tsc1 is a Critical Regulator of Macrophage Survival and Function Cellular Physiology and Biochemistry Macrophage mTOR Tsc1 |
| title | Tsc1 is a Critical Regulator of Macrophage Survival and Function |
| title_full | Tsc1 is a Critical Regulator of Macrophage Survival and Function |
| title_fullStr | Tsc1 is a Critical Regulator of Macrophage Survival and Function |
| title_full_unstemmed | Tsc1 is a Critical Regulator of Macrophage Survival and Function |
| title_short | Tsc1 is a Critical Regulator of Macrophage Survival and Function |
| title_sort | tsc1 is a critical regulator of macrophage survival and function |
| topic | Macrophage mTOR Tsc1 |
| url | http://www.karger.com/Article/FullText/430306 |
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