Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease
Background: Macrophage polarization plays a pivotal role in the process of inflammation which is common in chronic kidney disease (CKD). Macrophages polarization under the condition of CKD remains poorly understood. Here we tested the hypothesis that CKD promotes macrophage M1 polarization. Methods:...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2015-05-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430106 |
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| author | Cong Li Xiao Yan Ding Dong Mei Xiang Jie Xu Xiang Lan Huang Fan Fan Hou Qiu Gen Zhou |
| author_facet | Cong Li Xiao Yan Ding Dong Mei Xiang Jie Xu Xiang Lan Huang Fan Fan Hou Qiu Gen Zhou |
| author_sort | Cong Li |
| collection | DOAJ |
| description | Background: Macrophage polarization plays a pivotal role in the process of inflammation which is common in chronic kidney disease (CKD). Macrophages polarization under the condition of CKD remains poorly understood. Here we tested the hypothesis that CKD promotes macrophage M1 polarization. Methods: A rat model of CKD was established by reduced renal mass (RRM). Polarization of macrophages was induced in ex vivo macrophages from RRM rats and cultured ones under the condition of uremic serum. The markers were evaluated by RT-PCR, western blot, and flow cytometer. Results: Our data showed that macrophages from RRM rats displayed enhanced M1 and impaired M2 polarization as revealed by increased M1 markers (tumor necrosis factor α, IL-6, IL-12p40, nitric oxide) and decreased M2 markers (IL-10, CD206, arginase activity) in response to LPS and IL-4 induction, respectively. Treatment with uremic sera in peritoneal and bone marrow derived macrophages from normal rats led to similar results. Moreover, macrophages from RRM rats and cultured under the condition of uremic sera had reduced mitochondrial biogenesis. The disturbed macrophage polarization and mitochondrial biogenesis were accompanied by reduced activity of adenosine monophosphate-activated protein (AMP)-activated kinase (AMPK). Enhancing activation of AMPK restored mitochondrial biogenesis and M2 macrophage polarization. Conclusion: These observations suggest that CKD disturbs macrophage polarization and mitochondrial biogenesis through inhibition of AMPK. This might provide a novel therapeutic strategy for intervention of chronic inflammation in CKD. |
| first_indexed | 2024-12-11T00:38:52Z |
| format | Article |
| id | doaj.art-9fab58d3ec024b7fa4d3bdf4652ed544 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T00:38:52Z |
| publishDate | 2015-05-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-9fab58d3ec024b7fa4d3bdf4652ed5442022-12-22T01:27:01ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-05-0136135837210.1159/000430106430106Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney DiseaseCong LiXiao Yan DingDong Mei XiangJie XuXiang Lan HuangFan Fan HouQiu Gen ZhouBackground: Macrophage polarization plays a pivotal role in the process of inflammation which is common in chronic kidney disease (CKD). Macrophages polarization under the condition of CKD remains poorly understood. Here we tested the hypothesis that CKD promotes macrophage M1 polarization. Methods: A rat model of CKD was established by reduced renal mass (RRM). Polarization of macrophages was induced in ex vivo macrophages from RRM rats and cultured ones under the condition of uremic serum. The markers were evaluated by RT-PCR, western blot, and flow cytometer. Results: Our data showed that macrophages from RRM rats displayed enhanced M1 and impaired M2 polarization as revealed by increased M1 markers (tumor necrosis factor α, IL-6, IL-12p40, nitric oxide) and decreased M2 markers (IL-10, CD206, arginase activity) in response to LPS and IL-4 induction, respectively. Treatment with uremic sera in peritoneal and bone marrow derived macrophages from normal rats led to similar results. Moreover, macrophages from RRM rats and cultured under the condition of uremic sera had reduced mitochondrial biogenesis. The disturbed macrophage polarization and mitochondrial biogenesis were accompanied by reduced activity of adenosine monophosphate-activated protein (AMP)-activated kinase (AMPK). Enhancing activation of AMPK restored mitochondrial biogenesis and M2 macrophage polarization. Conclusion: These observations suggest that CKD disturbs macrophage polarization and mitochondrial biogenesis through inhibition of AMPK. This might provide a novel therapeutic strategy for intervention of chronic inflammation in CKD.http://www.karger.com/Article/FullText/430106MacrophagePolarizationMitochondrial biogenesisChronic inflammationChronic kidney disease |
| spellingShingle | Cong Li Xiao Yan Ding Dong Mei Xiang Jie Xu Xiang Lan Huang Fan Fan Hou Qiu Gen Zhou Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease Cellular Physiology and Biochemistry Macrophage Polarization Mitochondrial biogenesis Chronic inflammation Chronic kidney disease |
| title | Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease |
| title_full | Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease |
| title_fullStr | Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease |
| title_full_unstemmed | Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease |
| title_short | Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease |
| title_sort | enhanced m1 and impaired m2 macrophage polarization and reduced mitochondrial biogenesis via inhibition of amp kinase in chronic kidney disease |
| topic | Macrophage Polarization Mitochondrial biogenesis Chronic inflammation Chronic kidney disease |
| url | http://www.karger.com/Article/FullText/430106 |
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