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雷公藤甲素通过调节类风湿关节炎滑膜成纤维细胞中环氧合酶-2/前列腺素E2轴抑制Th17细胞分化

[Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/ prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis].

作者信息

Peng An-Ping, Wang Xiao-Yun, Zhuang Jun-Hua

出版信息

Zhongguo Zhong Yao Za Zhi. 2014 Feb;39(3):536-9.

PMID:24946563
Abstract

Triptolide (TPT), an active compound extracted from Chinese herb Tripterygium wilfordii , has been used in therapy of rheumatoid arthritis (RA). In this study, after synovial fibroblasts from rheumatoid arthritis (RASFs) were treated with TPT, we investigated its effect on the differentiation of Th17 cells. Firstly, the mRNA level of cyclooxygenase (COX) wad detected by qRT-PCR and the protein level of prostaglandin E2 (PGE2) was tested by ELISA in RASFs treated with different concentrations (0, 10, 50, 100 nmol L-1 ) of TPT. Then after TPT pre-treated RASFs and RA CD4 + T cells wer e co-cultured for 3 days in the presence or absence of PGE2, IL-17 and IFN-gamma production in CD4 T cell subsets were detected by flow cytometry. The results showed TPT decreased the mRNA experssion of COX2 and the secretion of PGE2 in RASFs in a dose-dependent manner(P <0. 05). We further found that differentiation of Thl7 cells was downregulated in a dose-dependent manner, and exogenous PGE2 could reverse the inhibition of Th17 cell differentiation(P <0. 05). Taken together, our results demonstrated that TPT inhibited the mRNA level of COX2 and the secretion of PGE2 in RASFs, which partly led to impaired Th17 cell differentiation in vitro.

摘要

雷公藤甲素(TPT)是从中药雷公藤中提取的一种活性化合物,已用于类风湿性关节炎(RA)的治疗。在本研究中,用TPT处理类风湿性关节炎滑膜成纤维细胞(RASFs)后,我们研究了其对Th17细胞分化的影响。首先,通过qRT-PCR检测不同浓度(0、10、50、100 nmol L-1)TPT处理的RASFs中环氧合酶(COX)的mRNA水平,并用ELISA检测前列腺素E2(PGE2)的蛋白水平。然后,在有或无PGE2的情况下,将TPT预处理的RASFs与RA CD4 + T细胞共培养3天,通过流式细胞术检测CD4 T细胞亚群中IL-17和IFN-γ的产生。结果表明,TPT以剂量依赖性方式降低RASFs中COX2的mRNA表达和PGE2的分泌(P <0.05)。我们进一步发现,Thl7细胞的分化以剂量依赖性方式下调,外源性PGE2可逆转对Th17细胞分化的抑制作用(P <0.05)。综上所述,我们的结果表明,TPT抑制RASFs中COX2的mRNA水平和PGE2的分泌,这在一定程度上导致体外Th17细胞分化受损。

相似文献

1
[Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/ prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis].雷公藤甲素通过调节类风湿关节炎滑膜成纤维细胞中环氧合酶-2/前列腺素E2轴抑制Th17细胞分化
Zhongguo Zhong Yao Za Zhi. 2014 Feb;39(3):536-9.
2
[Enhancement by FK506 of triptolide-induced inhibition of expression of COX-2 and iNOS in human rheumatoid arthritis synovial fibroblasts].[FK506增强雷公藤内酯醇对人类风湿关节炎滑膜成纤维细胞中COX-2和iNOS表达的抑制作用]
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003 Mar;35(3):277-82.
3
FK506 enhances triptolide-induced down-regulation of cyclooxygenase-2, inducible nitric oxide synthase as well as their products PGE2 and NO in TNF-alpha-stimulated synovial fibroblasts from rheumatoid arthritic patients.FK506增强雷公藤内酯醇诱导的类风湿关节炎患者肿瘤坏死因子-α刺激的滑膜成纤维细胞中环氧合酶-2、诱导型一氧化氮合酶及其产物前列腺素E2和一氧化氮的下调。
Eur J Med Res. 2005 Mar 29;10(3):110-6.
4
Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts.雷公藤内酯醇是从雷公藤中提取的一种新型二萜类三环氧化物,它能抑制人滑膜成纤维细胞中前基质金属蛋白酶1和3的产生及基因表达,并增强金属蛋白酶组织抑制剂1和2的产生及基因表达。
Arthritis Rheum. 2001 Sep;44(9):2193-200. doi: 10.1002/1529-0131(200109)44:9<2193::aid-art373>3.0.co;2-5.
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Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs.山奈酚抑制白细胞介素-1β诱导的类风湿关节炎滑膜成纤维细胞增殖及 COX-2、PGE2 和 MMPs 的产生。
Int J Mol Med. 2013 Oct;32(4):971-7. doi: 10.3892/ijmm.2013.1468. Epub 2013 Aug 9.
6
Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production.雷公藤提取物对环氧合酶2活性诱导及前列腺素E2生成的影响。
Arthritis Rheum. 1998 Jan;41(1):130-8. doi: 10.1002/1529-0131(199801)41:1<130::AID-ART16>3.0.CO;2-4.
7
Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23.滑膜成纤维细胞通过环氧化酶/前列腺素 E2 途径直接诱导 Th17 致病性,而不依赖于 IL-23。
J Immunol. 2013 Aug 1;191(3):1364-72. doi: 10.4049/jimmunol.1300274. Epub 2013 Jul 1.
8
Triptolide inhibits the differentiation of Th17 cells and suppresses collagen-induced arthritis.雷公藤甲素抑制Th17细胞分化并抑制胶原诱导的关节炎。
Scand J Immunol. 2008 Oct;68(4):383-90. doi: 10.1111/j.1365-3083.2008.02147.x.
9
Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells.雷公藤内酯醇通过抑制脂多糖处理的 PC12 细胞中 NF-κB 和 MAP 激酶的活性来下调 COX-2 的表达和 PGE2 的释放。
Phytother Res. 2012 Mar;26(3):337-43. doi: 10.1002/ptr.3538. Epub 2011 Jun 30.
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Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts.雷公藤甲素,一种从传统中药中鉴定出的活性化合物,可诱导类风湿性滑膜成纤维细胞凋亡。
BMC Pharmacol. 2004 Feb 17;4:2. doi: 10.1186/1471-2210-4-2.

引用本文的文献

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Tripterygium Ingredients for Pathogenicity Cells in Rheumatoid Arthritis.类风湿关节炎中雷公藤成分对致病细胞的作用
Front Pharmacol. 2020 Oct 2;11:583171. doi: 10.3389/fphar.2020.583171. eCollection 2020.
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Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications.用于哮喘炎症的草药:从基础研究到临床应用
Mediators Inflamm. 2016;2016:6943135. doi: 10.1155/2016/6943135. Epub 2016 Jul 20.
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Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review.雷公藤甲素的免疫抑制、抗炎及抗癌特性:一篇综述
Avicenna J Phytomed. 2016 Mar-Apr;6(2):149-64.