Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome
The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is the platform for IL-1β maturation, aimed at mediating a rapid immune response against danger signals which must be tightly regulated. Insulin is well known as the critical hormone in the maintenance of glucose in physiolog...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.587229/full |
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| author | Yu-Wei Chang Yu-Wei Chang Ling-Chien Hung Ling-Chien Hung Yu-Cheng Chen Yu-Cheng Chen Wen-Hung Wang Wen-Hung Wang Chun-Yu Lin Chun-Yu Lin Chun-Yu Lin Hsin-Han Tzeng Jau-Ling Suen Jau-Ling Suen Jau-Ling Suen Yen-Hsu Chen Yen-Hsu Chen Yen-Hsu Chen Yen-Hsu Chen |
| author_facet | Yu-Wei Chang Yu-Wei Chang Ling-Chien Hung Ling-Chien Hung Yu-Cheng Chen Yu-Cheng Chen Wen-Hung Wang Wen-Hung Wang Chun-Yu Lin Chun-Yu Lin Chun-Yu Lin Hsin-Han Tzeng Jau-Ling Suen Jau-Ling Suen Jau-Ling Suen Yen-Hsu Chen Yen-Hsu Chen Yen-Hsu Chen Yen-Hsu Chen |
| author_sort | Yu-Wei Chang |
| collection | DOAJ |
| description | The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is the platform for IL-1β maturation, aimed at mediating a rapid immune response against danger signals which must be tightly regulated. Insulin is well known as the critical hormone in the maintenance of glucose in physiologic response. Previous studies have proved insulin has the anti-inflammatory effect but the molecular mechanism of immunomodulation provided by insulin is not clear so far. Here we investigated whether insulin reduces inflammation by regulating the NLRP3 inflammasome. In the present study, we used LPS and ATP to induce the intracellular formation of the NLRP3 inflammasome. Insulin inhibited the secretion of IL-1β by preventing the assembly of the ASC in THP-1 cells and human CD14+ monocyte-derived macrophages. The phosphorylation status of Syk, p38 mitogen−activated protein kinase (MAPK) and ASC were altered by insulin. These effects were attenuated in THP-1 cells transfected with small interfering RNA targeting insulin receptors. In vivo, administration of glucose–insulin–potassium reduced serum IL-1β level, intestinal ASC speck formation, local macrophage infiltration and alleviated intestinal injury in mice exposed to LPS. Insulin may play an immunomodulatory role in anti-inflammation by regulating the NLRP3 inflammasome. |
| first_indexed | 2024-12-13T12:57:22Z |
| format | Article |
| id | doaj.art-d88312b5ef0a4a358d1f57a244801961 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T12:57:22Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d88312b5ef0a4a358d1f57a2448019612022-12-21T23:45:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.587229587229Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 InflammasomeYu-Wei Chang0Yu-Wei Chang1Ling-Chien Hung2Ling-Chien Hung3Yu-Cheng Chen4Yu-Cheng Chen5Wen-Hung Wang6Wen-Hung Wang7Chun-Yu Lin8Chun-Yu Lin9Chun-Yu Lin10Hsin-Han Tzeng11Jau-Ling Suen12Jau-Ling Suen13Jau-Ling Suen14Yen-Hsu Chen15Yen-Hsu Chen16Yen-Hsu Chen17Yen-Hsu Chen18College of Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Laboratory, Taitung Hospital, Ministry of Health and Welfare, Taitung, TaiwanDivision of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanSchool of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Research Center of Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanSchool of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Research Center of Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanSchool of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Research Center of Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, TaiwanCollege of Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanSchool of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Research Center of Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, TaiwanCollege of Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCollege of Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanResearch Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDivision of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanSchool of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Research Center of Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, TaiwanInstitute of Medical Science and Technology, National Sun-Yet University, Kaohsiung, TaiwanThe NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is the platform for IL-1β maturation, aimed at mediating a rapid immune response against danger signals which must be tightly regulated. Insulin is well known as the critical hormone in the maintenance of glucose in physiologic response. Previous studies have proved insulin has the anti-inflammatory effect but the molecular mechanism of immunomodulation provided by insulin is not clear so far. Here we investigated whether insulin reduces inflammation by regulating the NLRP3 inflammasome. In the present study, we used LPS and ATP to induce the intracellular formation of the NLRP3 inflammasome. Insulin inhibited the secretion of IL-1β by preventing the assembly of the ASC in THP-1 cells and human CD14+ monocyte-derived macrophages. The phosphorylation status of Syk, p38 mitogen−activated protein kinase (MAPK) and ASC were altered by insulin. These effects were attenuated in THP-1 cells transfected with small interfering RNA targeting insulin receptors. In vivo, administration of glucose–insulin–potassium reduced serum IL-1β level, intestinal ASC speck formation, local macrophage infiltration and alleviated intestinal injury in mice exposed to LPS. Insulin may play an immunomodulatory role in anti-inflammation by regulating the NLRP3 inflammasome.https://www.frontiersin.org/articles/10.3389/fimmu.2020.587229/fullinsulinnucleotide binding oligomerization domain (NOD)-LRR-and pyrin domain-containing protein 3 (NLRP3)inflammasomeASC |
| spellingShingle | Yu-Wei Chang Yu-Wei Chang Ling-Chien Hung Ling-Chien Hung Yu-Cheng Chen Yu-Cheng Chen Wen-Hung Wang Wen-Hung Wang Chun-Yu Lin Chun-Yu Lin Chun-Yu Lin Hsin-Han Tzeng Jau-Ling Suen Jau-Ling Suen Jau-Ling Suen Yen-Hsu Chen Yen-Hsu Chen Yen-Hsu Chen Yen-Hsu Chen Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome Frontiers in Immunology insulin nucleotide binding oligomerization domain (NOD)- LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome ASC |
| title | Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome |
| title_full | Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome |
| title_fullStr | Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome |
| title_full_unstemmed | Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome |
| title_short | Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome |
| title_sort | insulin reduces inflammation by regulating the activation of the nlrp3 inflammasome |
| topic | insulin nucleotide binding oligomerization domain (NOD)- LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome ASC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.587229/full |
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