{"title":"他克莫司(FK506)对人小胶质HMC3细胞系的抗炎和抗氧化作用","authors":"Fatma Gonca Kocanci, Azize Yasemin Goksu","doi":"10.1111/sji.13339","DOIUrl":null,"url":null,"abstract":"Abstract Microglial cells are indispensable for the normal development and functioning of neurons in the central nervous system, where they play a crucial role in maintaining brain homeostasis by surveilling the microenvironment for signs of injury or stress and responding accordingly. However, in neurodegenerative diseases, the density and phenotypes of microglial cells undergo changes, leading to chronic activation and inflammation. Shifting the focus from neurons to microglia in drug discovery for neurodegenerative diseases has become an important therapeutic target. This study was aimed to investigate the potential of Tacrolimus (FK506) an FDA‐approved calcineurin inhibitor, to modulate the pathology of neurodegenerative diseases through anti‐inflammatory and antioxidative effects on microglial activation. The human microglia clone 3 (HMC3) cells were exposed to 1 μg/mL LPS in the presence and absence of doses of FK506. Survival rates of cells were determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) method. Morphological evaluation of cells showed that FK506 restored the normal morphology of activated microglia. Furthermore, FK506 treatment increases the total antioxidant capacity and reduces the total oxidative capacity, indicating its potential antioxidant effects. Data from ELISA and RT‐PCR analyses showed that LPS abolished its promoting effects on the release of proinflammatory IL‐1β and IL‐6 cytokines in HMC3 cells, reflecting the anti‐inflammatory effect of FK506. These findings support the idea that FK506 could be a promising therapeutic agent for neurodegenerative diseases by modulating microglial activation and reducing inflammation and oxidative stress.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"126 49","pages":"0"},"PeriodicalIF":4.1000,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<scp>Anti‐inflammatory</scp> and <scp>antioxidative</scp> actions of tacrolimus (<scp>FK506</scp>) on human microglial <scp>HMC3</scp> cell line\",\"authors\":\"Fatma Gonca Kocanci, Azize Yasemin Goksu\",\"doi\":\"10.1111/sji.13339\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract Microglial cells are indispensable for the normal development and functioning of neurons in the central nervous system, where they play a crucial role in maintaining brain homeostasis by surveilling the microenvironment for signs of injury or stress and responding accordingly. However, in neurodegenerative diseases, the density and phenotypes of microglial cells undergo changes, leading to chronic activation and inflammation. Shifting the focus from neurons to microglia in drug discovery for neurodegenerative diseases has become an important therapeutic target. This study was aimed to investigate the potential of Tacrolimus (FK506) an FDA‐approved calcineurin inhibitor, to modulate the pathology of neurodegenerative diseases through anti‐inflammatory and antioxidative effects on microglial activation. The human microglia clone 3 (HMC3) cells were exposed to 1 μg/mL LPS in the presence and absence of doses of FK506. Survival rates of cells were determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) method. Morphological evaluation of cells showed that FK506 restored the normal morphology of activated microglia. Furthermore, FK506 treatment increases the total antioxidant capacity and reduces the total oxidative capacity, indicating its potential antioxidant effects. Data from ELISA and RT‐PCR analyses showed that LPS abolished its promoting effects on the release of proinflammatory IL‐1β and IL‐6 cytokines in HMC3 cells, reflecting the anti‐inflammatory effect of FK506. These findings support the idea that FK506 could be a promising therapeutic agent for neurodegenerative diseases by modulating microglial activation and reducing inflammation and oxidative stress.\",\"PeriodicalId\":21493,\"journal\":{\"name\":\"Scandinavian Journal of Immunology\",\"volume\":\"126 49\",\"pages\":\"0\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2023-11-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scandinavian Journal of Immunology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/sji.13339\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scandinavian Journal of Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/sji.13339","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Anti‐inflammatory and antioxidative actions of tacrolimus (FK506) on human microglial HMC3 cell line
Abstract Microglial cells are indispensable for the normal development and functioning of neurons in the central nervous system, where they play a crucial role in maintaining brain homeostasis by surveilling the microenvironment for signs of injury or stress and responding accordingly. However, in neurodegenerative diseases, the density and phenotypes of microglial cells undergo changes, leading to chronic activation and inflammation. Shifting the focus from neurons to microglia in drug discovery for neurodegenerative diseases has become an important therapeutic target. This study was aimed to investigate the potential of Tacrolimus (FK506) an FDA‐approved calcineurin inhibitor, to modulate the pathology of neurodegenerative diseases through anti‐inflammatory and antioxidative effects on microglial activation. The human microglia clone 3 (HMC3) cells were exposed to 1 μg/mL LPS in the presence and absence of doses of FK506. Survival rates of cells were determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) method. Morphological evaluation of cells showed that FK506 restored the normal morphology of activated microglia. Furthermore, FK506 treatment increases the total antioxidant capacity and reduces the total oxidative capacity, indicating its potential antioxidant effects. Data from ELISA and RT‐PCR analyses showed that LPS abolished its promoting effects on the release of proinflammatory IL‐1β and IL‐6 cytokines in HMC3 cells, reflecting the anti‐inflammatory effect of FK506. These findings support the idea that FK506 could be a promising therapeutic agent for neurodegenerative diseases by modulating microglial activation and reducing inflammation and oxidative stress.
期刊介绍:
This peer-reviewed international journal publishes original articles and reviews on all aspects of basic, translational and clinical immunology. The journal aims to provide high quality service to authors, and high quality articles for readers.
The journal accepts for publication material from investigators all over the world, which makes a significant contribution to basic, translational and clinical immunology.