Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases.
Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases.
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在神经炎症性疾病的背景下，芹菜素通过抑制RelB调节树突状细胞的活性并抑制炎症。
DOI：
10.1007/s11481-020-09933-8
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Jain P
中科院分区：
文献类型：
--
作者：
Ginwala R;Bhavsar R;Moore P;Bernui M;Singh N;Bearoff F;Nagarkatti M;Khan ZK;Jain P
神经炎症导致组织损伤，引起多发性硬化症的许多临床症状，多发性硬化症是一种中枢神经系统（CNS）的自身免疫性疾病。虽然T细胞，特别是Th1和Th17细胞是这种疾病的最终效应器，但树突状细胞（dc）介导T细胞的极化、活化等。在我们之前的研究中，芹菜素（Apigenin）是一种天然类黄酮，已被证明可以通过改善中枢神经系统脱髓鞘以及隔离DCs和其他外周髓系细胞来降低EAE疾病的严重程度。在这里，我们发现芹菜素可能通过将DC调节的t细胞反应从Th1和Th17型转变为Treg定向反应来发挥其作用，这可以通过在正常人类供体和EAE小鼠细胞中T-bet、IFN-γ (Th1)、IL-17 （Th17）的降低和IL-10、TGF-β和FoxP3 （Treg）表达的增加来证明。RelB是一种NF-κβ通路蛋白，是DC成熟、抗原呈递能力和DC介导的t细胞活化的核心。芹菜素降低RelB mRNA和蛋白水平，并减少其核易位。此外，sirna介导的RelB沉默进一步增强了RelB介导的芹菜素的作用，从而证实了它在芹菜素指导的DC生物学调控中的作用。这些结果为芹菜素调控DC活性的分子事件提供了关键信息，标志着其作为神经炎症性疾病治疗的潜力。
Neuroinflammation leads to tissue injury causing many of the clinical symptoms of Multiple Sclerosis, an autoimmune disorder of the central nervous system (CNS). While T cells, specifically Th1 and Th17 cells, are the ultimate effectors of this disease, dendritic cells (DCs) mediate T-cell polarization, activation, etc. In our previous study, Apigenin, a natural flavonoid, has been shown to reduce EAE disease severity through amelioration of demyelination in the CNS as well as the sequestering of DCs and other myeloid cells in the periphery. Here, we show that Apigenin exerts its effects possibly through shifting DC modulated T-cell responses from Th1 and Th17 type towards Treg directed responses evident through the decrease in T-bet, IFN-γ (Th1), IL-17 (Th17) and increase in IL-10, TGF-β and FoxP3 (Treg) expression in cells from both normal human donors and EAE mice. RelB, an NF-κβ pathway protein is central to DC maturation, its antigen presentation capabilities and DC-mediated T-cell activation. Apigenin reduced mRNA and protein levels of RelB and also reduced its nuclear translocation. Additionally, siRNA-mediated silencing of RelB further potentiated the RelB-mediated effects of Apigenin thus confirming its role in Apigenin directed regulation of DC biology. These results provide key information about the molecular events controlled by Apigenin in its regulation of DC activity marking its potential as a therapy for neuroinflammatory disease.
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影响因子：
3.7
作者：
Gentile D;Fornai M;Colucci R;Pellegrini C;Tirotta E;Benvenuti L;Segnani C;Ippolito C;Duranti E;Virdis A;Carpi S;Nieri P;Németh ZH;Pistelli L;Bernardini N;Blandizzi C;Antonioli L
通讯作者：
Antonioli L
影响因子：
8.4
作者：
Bruno, Andreina;Siena, Liboria;Pace, Elisabetta
通讯作者：
Pace, Elisabetta
影响因子：
4.7
作者：
Byun, Sanguine;Park, Jiman;Lee, Hyong Joo
通讯作者：
Lee, Hyong Joo
DOI：
10.1186/1476-9255-7-37
发表时间：
2010-07-27
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Jensen SS;Gad M
通讯作者：
Gad M
影响因子：
5.6
作者：
Kemanetzoglou E;Andreadou E
通讯作者：
Andreadou E