Upadhaya Puja, Lamenza Felipe F, Shrestha Suvekshya, Roth Peyton, Jagadeesha Sushmitha, Pracha Hasan, Horn Natalie A, Oghumu Steve
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA.
Antioxidants (Basel). 2023 Aug 24;12(9):1667. doi: 10.3390/antiox12091667.
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 OVA 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.
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，迄今为止，针对浆果活性成分在缓解接触性超敏反应（CHS）这一最常见的职业性皮肤病方面的作用所开展的研究有限。我们的研究涉及一项体外研究，旨在评估黑树莓提取物（BRB-E）以及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。我们检测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（DCs）活化的功效。具体而言，我们测量了活化标志物CD40、CD80、CD83和CD86的表达以及促炎细胞因子的产生，包括白细胞介素（IL）-12、IL-6、肿瘤坏死因子-α和IL-10，以获得更深入的了解。通过研究磷酸化细胞外信号调节激酶（phospho-ERK）的作用，还探究了这些植物化学物质减轻CHS的潜在机制。随后，将DCs与OVA肽特异性T细胞共培养，以检测这些相互作用产生的特异性T细胞效应反应。我们的研究结果表明，BRB-E、PCA、PANT和EA，但不包括KMP，可抑制LPS活化的DCs中ERK的磷酸化。在较高剂量下，EA显著降低了DNFB和LPS刺激的DCs中所研究的所有活化标志物的表达。所有测试化合物均降低了Flt3L中以及GM-CSF来源的DCs中DNFB刺激的DCs中IL-6的水平。然而，在LPS刺激的Flt3L来源的骨髓来源DCs（BMDCs）中，所有测试化合物均降低了IL-12的水平。PCA、PANT、EA和KMP抑制活化的DC介导的T细胞产生干扰素（IFN）-γ和IL-17。有趣的是，PANT、EA和KMP显著降低了T细胞增殖以及相关的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活化的DCs的不同作用提供了证据，揭示了减轻CHS的潜在新方法。
