Anti‐inflammatory and antioxidative actions of tacrolimus (FK506) on human microglial HMC3 cell line

IF 4.1 4区 医学 Q2 IMMUNOLOGY
Fatma Gonca Kocanci, Azize Yasemin Goksu
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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.

Abstract Image

他克莫司(FK506)对人小胶质HMC3细胞系的抗炎和抗氧化作用
小胶质细胞对中枢神经系统神经元的正常发育和功能至关重要,它们通过监测微环境中损伤或应激的迹象并做出相应的反应,在维持大脑稳态中起着至关重要的作用。然而,在神经退行性疾病中,小胶质细胞的密度和表型发生变化,导致慢性激活和炎症。将神经退行性疾病药物开发的重点从神经元转移到小胶质细胞已成为一个重要的治疗目标。本研究旨在探讨FDA批准的钙调神经磷酸酶抑制剂他克莫司(FK506)通过对小胶质细胞激活的抗炎和抗氧化作用来调节神经退行性疾病病理的潜力。人小胶质细胞克隆3 (HMC3)细胞在FK506存在和不存在剂量的情况下暴露于1 μg/mL LPS。采用3‐(4,5‐二甲基噻唑‐2‐基)‐2,5‐二苯基溴化四唑(MTT)法测定细胞存活率。细胞形态学评价显示,FK506恢复了激活小胶质细胞的正常形态。此外,FK506处理提高了总抗氧化能力,降低了总氧化能力,表明其潜在的抗氧化作用。ELISA和RT - PCR分析结果显示,LPS对HMC3细胞促炎IL - 1β和IL - 6细胞因子释放的促进作用被消除,反映了FK506的抗炎作用。这些发现支持了FK506可能通过调节小胶质细胞激活和减少炎症和氧化应激而成为一种有前途的神经退行性疾病治疗剂的观点。
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来源期刊
CiteScore
7.70
自引率
5.40%
发文量
109
审稿时长
1 months
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.
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