Scutellaria extract and wogonin inhibit tumor-mediated induction of T(reg) cells via inhibition of TGF-β1 activity.
Scutellaria extract and wogonin inhibit tumor-mediated induction of T(reg) cells via inhibition of TGF-β1 activity.
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DOI：
10.1007/s00262-011-1130-3
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发表时间：
2012-05
影响因子：
5.8
通讯作者：
Parajuli, Prahlad
中科院分区：
文献类型：
--
作者：
Dandawate, Sagar;Williams, Linford;Joshee, Nirmal;Rimando, Agnes M.;Mittal, Sandeep;Thakur, Archana;Lum, Lawrence G.;Parajuli, Prahlad
许多研究表明肿瘤诱导的 Treg 细胞活性与治疗性疫苗的次优反应有关。因此，开发针对 Treg 细胞的新佐剂策略势在必行。在临床前和临床研究中，黄芩提取物或黄酮类成分已显示出对抗各种肿瘤（包括神经胶质瘤）的令人鼓舞的功效。我们在此首次报道黄芩叶提取物 (SocL) 和类黄酮汉黄芩素可以抑制恶性胶质瘤中 TGF-β1 诱导的 Treg 活性。皮下移植 F98 神经胶质瘤的 F344 大鼠接受 SocL 治疗。与对照组相比，SocL 治疗动物的肿瘤内 TGF-β1 和 Treg 细胞频率以及外周血 TGF-β1 水平均受到显着抑制。 SocL 提取物和汉黄芩素还在体外抑制神经胶质瘤诱导的、TGF-β1 介导的 Treg 活性。 SocL 提取物和汉黄芩素还抑制 Treg 培养物中 IL-10 的分泌；而IL-2的水平要么没有变化，要么略有提高。我们还观察到Treg细胞中SocL和汉黄芩素对Smad-3、GSK-3β和ERK1/2信号传导的抑制，而P38 MAPK的磷酸化显着增强，表明SocL或汉黄芩素可以通过调节Smad和非Smad信号通路抑制T细胞对TGF-β1的反应。总体而言，这项研究表明黄芩可以通过抑制 TGF-β1 分泌以及抑制 T 细胞对 TGF-β1 的反应来逆转肿瘤介导的免疫抑制。这可能为开发一种新的恶性胶质瘤辅助治疗策略提供机会，将黄芩与免疫疗法和化疗/放射治疗方案相结合，这可能会改善疾病的结果。
A number of studies have implicated tumor-induced Treg cell activity in the sub-optimal response to therapeutic vaccines. Development of neo-adjuvant strategies targeting Treg cells is therefore imperative. Scutellaria extracts or constituent flavonoids have shown encouraging efficacy against various tumors, including gliomas, in both pre-clinical and clinical studies. We report here, for the first time, that Scutellaria ocmulgee leaf extract (SocL) and flavonoid wogonin could inhibit TGF-β1-induced Treg activity in malignant gliomas. F344 rats, subcutaneously transplanted with F98 gliomas, were treated with SocL. There was a significant inhibition of intra-tumoral TGF-β1 and Treg cell frequency as well as peripheral blood TGF-β1 levels in SocL-treated animals compared to the controls. SocL extract and wogonin also inhibited glioma-induced, TGF-β1-mediated Treg activity in vitro. SocL extract and wogonin also inhibited the secretion of IL-10 in Treg culture; whereas the level of IL-2 was either unchanged or marginally enhanced. We also observed an inhibition of Smad-3, GSK-3β and ERK1/2 signaling by SocL and wogonin in Treg cells, while phosphorylation of P38 MAPK was considerably enhanced, indicating that SocL or wogonin could inhibit the T cells’ response to TGF-β1 via modulation of both Smad and non-Smad signaling pathways. Overall, this study suggests that Scutellaria can potentially reverse tumor-mediated immune suppression via inhibition of TGF-β1 secretion as well as via inhibition of T cells’ response to TGF-β1. This may provide an opportunity for developing a novel adjuvant therapeutic strategy for malignant gliomas, combining Scutellaria with immunotherapy and chemo/radio-therapeutic regimen, which could potentially improve the disease outcome.
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DOI：
10.4049/jimmunol.0804074
发表时间：
2009-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacob JB;Kong YC;Nalbantoglu I;Snower DP;Wei WZ
通讯作者：
Wei WZ
影响因子：
14.8
作者：
Fantini, Massimo C.;Dominitzki, Sabine;Becker, Christoph
通讯作者：
Becker, Christoph
影响因子：
11.2
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.
影响因子：
3.4
作者：
Burdette-Radoux, S;Tozer, RG;Eisenhauer, EA
通讯作者：
Eisenhauer, EA
影响因子：
11.2
作者：
Domschke, Christoph;Schuetz, Florian;Beckhove, Philipp
通讯作者：
Beckhove, Philipp