Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling.
Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling.
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DOI：
10.1007/s00262-014-1564-5
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发表时间：
2014-09
影响因子：
5.8
通讯作者：
Lesinski, Gregory B.
中科院分区：
文献类型：
--
作者：
Mace, Thomas A.;King, Samantha A.;Ameen, Zeenath;Elnaggar, Omar;Young, Gregory;Riedl, Kenneth M.;Schwartz, Steven J.;Clinton, Steven K.;Knobloch, Thomas J.;Weghorst, Christopher M.;Lesinski, Gregory B.
来自天然产品的生物活性植物化学物质，如黑覆盆子（BRB; Rubus occidentalis）在培养和异种移植模型中对恶性细胞具有直接的抗癌特性。在更复杂的啮齿动物致癌模型中，BRB成分抑制癌症进展。虽然癌细胞中BRB植物化学物质的机制靶点开始出现，但其在调节影响癌症的宿主免疫过程中的潜在作用尚未得到系统的研究。我们假设BRB含有能够激发有效免疫调节特性的化合物，这些特性可以影响与慢性炎症和肿瘤进展相关的细胞介质。我们研究了含有多种植物化学物质的黑树莓乙醇提取物（BRB- e）和摄入后产生的两种丰富的BRB植物化学代谢物（Cyanidin-3-Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R）。BRB-E抑制CD3/CD28激活的人CD4+和CD8+ T淋巴细胞的增殖和活力。BRB-E还限制了髓源性抑制细胞（MDSC）的体外扩增及其抑制能力。用BRB-E预处理免疫细胞可减弱il -6介导的信号转导和转录激活因子3 （STAT3）的磷酸化，而IL-2可诱导STAT5的磷酸化。相比之下，用C3R和Q3R代谢物预处理免疫细胞可抑制MDSC扩增、il -6介导的STAT3信号传导，但不能抑制IL-2诱导的STAT5磷酸化，并且对T细胞活力的抑制作用较弱。总之，这些数据表明，BRB提取物及其生理相关代谢物含有植物化学物质，影响与致癌和免疫治疗相关的免疫过程。此外，特定的BRB成分及其代谢物可能是药物开发先导化合物的来源，这些先导化合物表现出靶向免疫结果或抑制特定的stat调节信号通路。
Bioactive phyotochemicals from natural products, such as black raspberries (BRB; Rubus occidentalis) have direct anti-cancer properties on malignant cells in culture and in xenograft models. BRB components inhibit cancer progression in more complex rodent carcinogenesis models. Although mechanistic targets for BRB phytochemicals in cancer cells are beginning to emerge, the potential role in modulating host immune processes impacting cancer have not been systematically examined. We hypothesized that BRB contain compounds capable of eliciting potent immunomodulatory properties that impact cellular mediators relevant to chronic inflammation and tumor progression. We studied both an ethanol extract from black raspberries (BRB-E) containing a diverse mixture of phytochemicals and two abundant phytochemical metabolites of BRB produced upon ingestion (Cyanidin-3-Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R). BRB-E inhibited proliferation and viability of CD3/CD28 activated human CD4+ and CD8+ T lymphocytes. BRB-E also limited in vitro expansion of myeloid-derived suppressor cells (MDSC) and their suppressive capacity. Pre-treatment of immune cells with BRB-E attenuated IL-6-mediated phosphorylation of signal transducer and activator of transcription-3 (STAT3) and IL-2 induced STAT5 phosphorylation. In contrast, pre-treatment of immune cells with the C3R and Q3R metabolites inhibited MDSC expansion, IL-6-mediated STAT3 signaling, but not IL-2 induced STAT5 phosphorylation and were less potent inhibitors of T cell viability. Together these data indicate that BRB extracts and their physiologically-relevant metabolites contain phytochemicals that affect immune processes relevant to carcinogenesis and immunotherapy. Furthermore, specific BRB components and their metabolites may be a source of lead compounds for drug development that exhibit targeted immunological outcomes or inhibition of specific STAT-regulated signaling pathways.
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影响因子：
2.9
作者：
Lechner, John F.;Reen, Rashmeet K.;Stoner, Gary D.
通讯作者：
Stoner, Gary D.
影响因子：
2.9
作者：
Erlund, Iris;Freese, Riitta;Alfthan, Georg
通讯作者：
Alfthan, Georg
DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
6.1
作者：
Choi, Jung-Suk;Kang, Sang-Wook;Kang, Young-Hee
通讯作者：
Kang, Young-Hee
在合成生物学时代，用于癌症免疫疗法的过继T细胞转移。
影响因子：
32.4
作者：
Kalos M;June CH
通讯作者：
June CH