Pimecrolimus protects neuron‐like SH‐SY5Y cells against anti‐inflammatory and anti‐oxidant effects of both microglial secretome and hydrogen peroxide

IF 4.1 4区 医学 Q2 IMMUNOLOGY
Fatma Gonca Kocanci, Azize Yasemin Goksu Erol, Fatma Yildiz, Hamiyet Eciroglu
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Abstract

Abstract Calcineurin inhibitors have been found to exhibit a preventive role against neuroinflammation, which represents a crucial underlying mechanism in neurodegenerative diseases (ND). Additionally, they possess suppressive effects on the activation of apoptotic pathways, which constitute another mechanism underlying such diseases. Given that pimecrolimus, a calcineurin inhibitor, impedes the synthesis of pro‐inflammatory cytokines, such as interleukin (IL)‐2, IL‐4, and IL‐10, and influences apoptotic processes, it is noteworthy to test its potential neuroprotective properties. Thus, the objective of this investigation was to assess the potential protective effects of pimecrolimus against the degenerative consequences of both microglial secretomes and hydrogen peroxide (H 2 O 2 ), an oxidant agent. The survival rates of HMC3 microglia cells, neuron‐like differentiated SH‐SY5Y (d‐SH‐SY5Y) cells, and their co‐culture were determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) method. Furthermore, the levels of pro‐inflammatory cytokines IL‐1β and IL‐6, and anti‐inflammatory cytokine IL‐10 were measured using ELISA kits, besides total antioxidant and oxidant capacities in conditioned media of cells. Additionally, the effect of pimecrolimus on neurite length in these cell groups was evaluated through morphological observations. This study revealed, for the first time, that pimecrolimus exerts preventive effects on neurodegenerative processes by virtue of its anti‐inflammatory and ‐antioxidant activities. It holds promise as a potential treatment option for ND.
吡美莫司保护神经元样SH - SY5Y细胞免受小胶质分泌组和过氧化氢的抗炎和抗氧化作用
钙调磷酸酶抑制剂已被发现对神经炎症具有预防作用,这代表了神经退行性疾病(ND)的重要潜在机制。此外,它们对凋亡通路的激活具有抑制作用,这构成了此类疾病的另一机制。考虑到吡美莫司,一种钙调磷酸酶抑制剂,阻碍了促炎细胞因子的合成,如白细胞介素(IL) - 2、IL - 4和IL - 10,并影响细胞凋亡过程,值得注意的是测试其潜在的神经保护特性。因此,本研究的目的是评估吡美莫司对小胶质分泌体和过氧化氢(h2o2)(一种氧化剂)退行性后果的潜在保护作用。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HMC3小胶质细胞、神经元样分化的SH‐SY5Y (d‐SH‐SY5Y)细胞及其共培养细胞的存活率。此外,使用ELISA试剂盒检测促炎细胞因子IL - 1β和IL - 6的水平,以及抗炎细胞因子IL - 10的水平,以及细胞条件培养基中的总抗氧化能力和氧化能力。此外,通过形态学观察评估吡美莫司对这些细胞组神经突长度的影响。这项研究首次揭示了吡美莫司通过其抗炎和抗氧化活性对神经退行性过程具有预防作用。它有望成为ND的潜在治疗选择。
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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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