Berry Extracts and Their Bioactive Compounds Mitigate LPS and DNFB-Mediated Dendritic Cell Activation and Induction of Antigen Specific T-Cell Effector Responses.

Berry Extracts and Their Bioactive Compounds Mitigate LPS and DNFB-Mediated Dendritic Cell Activation and Induction of Antigen Specific T-Cell Effector Responses.
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DOI:
10.3390/antiox12091667
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发表时间:
2023-08-24
期刊:
Antioxidants (Basel, Switzerland)
影响因子:
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其他
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浆果因其丰富的天然抗氧化、抗炎和免疫调节特性而获得广泛认可。然而,到目前为止,已经进行了有限的研究,以调查浆果的活性成分在减轻接触性超敏反应(CHS),最流行的职业性皮肤病的作用。我们的研究涉及离体调查,旨在评估黑树莓提取物(BRB-E)和浆果中发现的各种天然化合物,如原儿茶酸(PCA),原花青素(PANT),鞣花酸(EA)和山奈酚(KMP)对减轻CHS致病性的影响。我们研究了这些天然化合物对由2,4-二硝基氟苯(DNFB)和脂多糖(LPS)触发的树突状细胞(DC)活化的功效。具体而言,我们测量了活化标志物CD 40、CD 80、CD 83和CD 86的表达以及促炎细胞因子(包括白细胞介素(IL)-12、IL-6、TNF-α和IL-10)的产生,以获得进一步的了解。通过研究磷酸化ERK的作用,这些植物化学物质可以减轻CHS的潜在机制也进行了研究。随后,将DC与特异于OVA 323 -339肽的T细胞共培养,以检查由这些相互作用引起的特异性T细胞效应子应答。我们的研究结果表明,BRB-E,PCA,PANT和EA,但不KMP,抑制ERK在LPS激活的DC的磷酸化。在较高剂量下,EA显着降低DNFB和LPS刺激的DC中研究的所有活化标志物的表达。所有测试的化合物降低Flt 3L中DNFB刺激的DC以及GM-CSF衍生的DC中的IL-6水平。然而,在LPS刺激的Flt 3L衍生的BMDC中,IL-12的水平被所有测试化合物降低。PCA、PANT、EA和KMP抑制DC介导的T细胞产生IFN-γ和IL-17。有趣的是,PANT、EA和KMP显著降低T细胞增殖和相关的IL-2产生。我们的研究为浆果提取物和天然化合物对DNFB和LPS激活的DC的不同作用提供了证据,揭示了缓解CHS的潜在新方法。
Berries have gained widespread recognition for their abundant natural antioxidant, anti-inflammatory, and immunomodulatory properties. However, there has been limited research conducted thus far to investigate the role of the active constituents of berries in alleviating contact hypersensitivity (CHS), the most prevalent occupational dermatological disease. Our study involved an ex vivo investigation aimed at evaluating the impact of black raspberry extract (BRB-E) and various natural compounds found in berries, such as protocatechuic acid (PCA), proanthocyanidins (PANT), ellagic acid (EA), and kaempferol (KMP), on mitigating the pathogenicity of CHS. We examined the efficacy of these natural compounds on the activation of dendritic cells (DCs) triggered by 2,4-dinitrofluorobenzene (DNFB) and lipopolysaccharide (LPS). Specifically, we measured the expression of activation markers CD40, CD80, CD83, and CD86 and the production of proinflammatory cytokines, including Interleukin (IL)-12, IL-6, TNF-α, and IL-10, to gain further insights. Potential mechanisms through which these phytochemicals could alleviate CHS were also investigated by investigating the role of phospho-ERK. Subsequently, DCs were co-cultured with T-cells specific to the OVA323-339 peptide to examine the specific T-cell effector responses resulting from these interactions. Our findings demonstrated that BRB-E, PCA, PANT, and EA, but not KMP, inhibited phosphorylation of ERK in LPS-activated DCs. At higher doses, EA significantly reduced expression of all the activation markers studied in DNFB- and LPS-stimulated DCs. All compounds tested reduced the level of IL-6 in DNFB-stimulated DCs in Flt3L as well as in GM-CSF-derived DCs. However, levels of IL-12 were reduced by all the tested compounds in LPS-stimulated Flt3L-derived BMDCs. PCA, PANT, EA, and KMP inhibited the activated DC-mediated Interferon (IFN)-γ and IL-17 production by T-cells. Interestingly, PANT, EA, and KMP significantly reduced T-cell proliferation and the associated IL-2 production. Our study provides evidence for differential effects of berry extracts and natural compounds on DNFB and LPS-activated DCs revealing potential novel approaches for mitigating CHS.
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发表时间: 2020-09-07
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