Mechanisms by which TLR4 and endotoxin promote hepatocellular carcinoma require further investigation

Mencin, Ali; Gwak, Geum‐Youn; Schwabe, Robert F.

doi:10.1002/hep.24408

Cited by 3 publications

(2 citation statements)

References 45 publications

(61 reference statements)

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“…It was reported that IL-10 might have a crucial role in the progression of liver fibrosis [ 28 , 29 ], which was also consistent with our present study. In the present study, there was a lower level of IL-10 in the supernatant when human stellate cells were treated with PBMCs from PBC patients than from the HCs.…”

Section: Discussionsupporting

confidence: 94%

Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis

et al. 2017

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Regulatory T cells (Tregs) play an indispensable role in the progression of primary biliary cholangitis (PBC). Although Tregs could normalize costimulation in in vivo and in vitro models, it is obscure whether and how Tregs mediate these effects in PBC. Herein we focused on the quantitative and functional characteristics of Tregs in PBC. The number and proportion of Tregs, and the production of interleukin (IL)-10 were all significantly less in the PBC patients than in the healthy controls (HCs). In addition, compared to the HCs, the costimulatory CD86 of the circulation and liver were significantly higher in the patients with PBC. CD86 expression on CD1c+ cells negatively correlated with the proportion of Tregs. There was also a positive correlation between mayo risk score and the ratio of CD86/Treg. In vitro experiments showed that inhibition of CD86 expression on CD1c+ cells by Tregs was significantly weakened in the PBC patients. Furthermore, the autoantibodies from the PBC patients could promote CD86 expression on CD1c+ cells and transforming growth factor-β production by human hepatic stellate cells. Overall, Tregs declined in inhibition on co-stimulation expression in the presence of autoantibodies, which could be associated to PBC-related bile duct injury and fibrosis. This indicated that maintenance of balance of co-stimulation and Tregs could be beneficial for PBC.

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Section: Discussionsupporting

confidence: 94%

Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis

et al. 2017

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“…The TLR4/MyD88/TAK1 complex, a key upstream pathway, regulates relative level of inflammation induced by LPS via activation of the NF-κB, p65 and MAPK pathways, which have been regarded as important targets for inhibition by various drugs [26]. Lipopolysaccharide (LPS) significantly activates inflammatory pathways by binding TLR4, and TLR4 mediates activation of NF-κB/MAPK pathway, thereby producing inflammatory responses [27].…”

Section: Discussionmentioning

confidence: 99%

Engelharquinone suppresses lipopolysaccharide-induced inflammation and proliferation of human liver cancer SMCC7721 cells via inhibition of NF-κB and MAPK signaling pathway

Li¹,

Zhang²,

Gao³

et al. 2020

Trop. J. Pharm Res

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Purpose: To investigate the anti-tumor effect of engelharquinone (Eng) on human liver cancer SMCC7721 cells.Methods: GFP-labeled SMCC7721 cells were used to establish a tumor-bearing mice model used for determination of the effect of different concentrations of Eng on tumor growth. The effect of Eng on SMCC7721 cell viability was determined with MTT assay and cell cycle analysis. The anti-inflammatory effect of Eng on lipopolysaccharide (LPS)-treated SMCC7721 cells were determined through assay of pro-inflammatory cytokines. Besides, the effect of Eng on the expressions of mitogen-activated protein kinase (MAPK), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) was determined.Results: Cell proliferation was suppressed by different concentrations of Eng in LPS-treated SMCC7721 cells. Treatment of nude mice with Eng at high and low doses resulted in significant suppression of tumor growth and marked increases in percentage survival. Treatment of SMCC7721 cells with LPS upregulated the expressions of NF-κB, p65 and MAPK. However, pre-treatment of the cells with Eng suppressed the LPS-induced upregulation of the NF-κB, p65 and MAPK signaling pathways, and further downregulated the production of inflammatory cytokines in SMCC7721 cells.Conclusion: These results indicate that Eng inhibits LPS-induced inflammation and proliferation of human liver cancer SMCC7721 cells via a mechanism involving regulation of NF-κB and MAPK signaling pathways. Thus, Eng has potentials for the clinical management of inflammatory diseases and liver cancer. Keywords: Inflammation, Engelharquinone, Lipopolysaccharide, SMCC7721 cells, Toll-like receptor 4

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Intestinal Microbiome and the Liver

Gillevet¹,

Puri²

2018

Zakim and Boyer's Hepatology

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Mechanisms by which TLR4 and endotoxin promote hepatocellular carcinoma require further investigation

Cited by 3 publications

References 45 publications

Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis

Regulatory T cells with a defect in inhibition on co-stimulation deteriorated primary biliary cholangitis

Engelharquinone suppresses lipopolysaccharide-induced inflammation and proliferation of human liver cancer SMCC7721 cells via inhibition of NF-κB and MAPK signaling pathway

Intestinal Microbiome and the Liver

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