Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway

Wu, Xin; Dou, Youjun; Yang, Yan; Bian, Difei; Luo, Jun; Tong, Bei; Xia, Yufeng; Dai, Yue

doi:10.1016/j.bcp.2015.06.008

Cited by 51 publications

(30 citation statements)

References 36 publications

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“…Previously, we confirmed that arctigenin inhibited the differentiation of Th17 cells and thereby attenuated colitis by restricting the activation of mTORC1 [2]. To define whether ERs play a pivotal role in the inhibition of arctigenin on mTORC1-mediated Th17 cell differentiation, we treated naïve T cells with MPP, PHTPP, G15 and ICI in the presence or absence of arctigenin or E2 under Th17-polarizing cocktails.…”

Section: Resultsmentioning

confidence: 93%

“…After treatment for three days, the cells were harvested for analysis. The frequencies of Th17 cells were analyzed by flow cytometry as previously described [2]. …”

Section: Methodsmentioning

confidence: 99%

“…Quantitative PCR was performed as previously described [2]. The primer sequences in the reaction used were listed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we reported that arctigenin, a dibenzylbutyrolactone lignan constituent of Fructus Arctii (a traditional Chinese medicine), could effectively ameliorate the colonic inflammation and crypt damage in dextran sulfate sodium (DSS)-induced colitis in mice, and it functioned mainly by inhibiting the differentiation of Th17 cells via down-regulation of the activation of mTORC1. Of note, the inhibitory effect of arctigenin on mTORC1 activation was independent on the classical upstream pathways of mTORC1 signaling [2, 3], and its potential target protein and underlying mechanism remained to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation

Tong

Yang

et al. 2016

Oncotarget

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Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ERβ largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ERβ-dependent manner. Moreover, arctigenin was recognized to be an agonist of ERβ, which could bind to ERβ with a moderate affinity, promote dissociation of ERβ/HSP90 complex and nuclear translocation and phosphorylation of ERβ, and increase the transcription activity. Following activation of ERβ, arctigenin inhibited the activity of mTORC1 by disruption of ERβ-raptor-mTOR complex assembly. Deficiency of ERβ markedly abolished arctigenin-mediated inhibition of Th17 cell differentiation. In colitis mice, the activation of ERβ, inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by PHTPP treatment. In conclusion, ERβ might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development.

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Section: Resultsmentioning

confidence: 93%

“…After treatment for three days, the cells were harvested for analysis. The frequencies of Th17 cells were analyzed by flow cytometry as previously described [2]. …”

Section: Methodsmentioning

confidence: 99%

“…Quantitative PCR was performed as previously described [2]. The primer sequences in the reaction used were listed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation

Tong

Yang

et al. 2016

Oncotarget

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“…mTORC1 also promotes the nucleus translocation RORgt, a major transcription factor of Th17 [56]. Treatment with arctigenin, a chemical inhibitor of mTORC1, inhibits the Th1 and Th17 differentiation [57]. Using a T-cell-specific deletion of the Raptor model, another group observed that the loss of mTORC1 restricts Th2 differentiation [58].…”

Section: Key Metabolic Checkpoints Of T Cell Immunitymentioning

confidence: 99%

Regulation of T cell immunity by cellular metabolism

Zou

2018

Front. Med.

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T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

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Asiaticoside hinders the invasive growth of keloid fibroblasts through inhibition of the GDF‐9/MAPK/Smad pathway

Bian

Dou

et al. 2017

J Biochem & Molecular Tox

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Higher expression of growth differentiation factor-9 (GDF-9) in keloids compared with hypertrophic scars and normal skin tissues has been reported recently. The present study was performed to investigate the role of GDF-9 in keloid pathogenesis, and to elucidate its implication for asiaticoside in the keloid management. The data showed that GDF-9 could enhance the proliferation, migration, and invasion of keloid fibroblasts (KFs), while it only slightly elevated collagen expression, indicating that the effect of GDF-9 was opposite to that of TGF-β1. The bioactivity difference between GDF-9 and TGF-β1 could be explained by the different phosphorylated sites on the downstream Smad2/3. Moreover, asiaticoside could inhibit GDF-9-induced activation of MAPKs and Smad pathway in KFs. In conclusion, GDF-9 enhanced the invasive growth of KFs, which was achieved by phosphorylation of Smad 2/3 at the linker region through activation of MAPKs pathway. Asiaticoside hindered the invasive growth of KFs by inhibiting the GDF-9/MAPK/Smad pathway.

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Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway

Cited by 51 publications

References 36 publications

Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation

Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation

Regulation of T cell immunity by cellular metabolism

Asiaticoside hinders the invasive growth of keloid fibroblasts through inhibition of the GDF‐9/MAPK/Smad pathway

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