IL-6 pathway in the liver: From physiopathology to therapy

Schmidt-Arras, Dirk; Rose-John, Stefan

doi:10.1016/j.jhep.2016.02.004

Cited by 675 publications

(578 citation statements)

References 124 publications

Supporting

Mentioning

510

Contrasting

Unclassified

Order By: Relevance

“…In our evaluation, we noticed an increase in the recruitment of proinflammatory cells with a concomitant increment in inflammatory markers, altogether suggesting that aging may promote a moderate proinflammatory status in the liver. Kupffer cells isolated from aged rats displayed high IL‐6 levels, which could possibly reflect beneficial effects of IL‐6 on liver regeneration, infection defense, and regulation of metabolic functions (Schmidt‐Arras & Rose‐John, 2016), while traditional “polarization markers” of hepatic macrophages (Krenkel & Tacke, 2017) were not dramatically altered. However, given the complexity of inflammation and immune cell subsets, further investigations are required to define, which inflammatory processes are functionally relevant during aging.…”

Section: Discussionmentioning

confidence: 99%

Effects of aging on liver microcirculatory function and sinusoidal phenotype

et al. 2018

View full text Add to dashboard Cite

The socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of aging on liver microcirculatory function and sinusoidal phenotype

et al. 2018

View full text Add to dashboard Cite

show abstract

“…This effect may counteract the apoptosis induced by the overexpression of a1-ACT in the liver during the acute-phase response.IL-6 binds to the IL-6 receptor (IL-6R) and leads to the activation of the tyrosine kinase JAK1, which induces the activation of several intracellular signalling pathways,including the MAPK and PI3K pathway. This may offset the inhibitory effect ofa1-ACT on the PI3K/AKT/mTOR signalling pathway [53]. …”

Section: Discussionmentioning

confidence: 99%

Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN

Zhu¹,

Liu²,

Tang³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background & Aims: To investigate the expression and prognostic value of α1-ACT (Alpha1-antichymotrypsin) in patients with HCC (hepatocellular carcinoma) and identify the mechanism by which α1-ACT inhibits proliferation and promotes apoptosis of HCC. Methods: We first measured α1-ACT expression levels and determined their relationship with the clinicopathological characteristics and prognosis of patients with HCC.We then established stable HCC cell lines with both α1-ACT overexpression and knockdown and performed a functional analysis in vitro.We first examined the relationship between α1-ACT and the PTEN/PI3K/AKT/mTOR pathway using Western blotting. Then, we determined whether α1-ACT can directly bind to PTEN using co-immunoprecipitation. Finally, we measured α1-ACT expression to evaluate its correlation with the PI3K/AKT/mTOR pathway-related apoptosis proteins in a xenograft tumour mouse model using immunohistochemistry. Results: The α1-ACT expression level was significantly lower in the HCC tissues than in the paratumour tissues and was negatively positively correlated with the level of Ki67, AFP, the AJCC stage, tumour size and tumour invasion. The overexpression of α1-ACT can inhibit cell proliferation and increase cell apoptosis by activating PI3K/AKT/mTOR-mediated apoptosis via binding to PTEN and activating it in vitro. Additionally, the overexpression of α1-ACT can also increase the proportion of cells in the G0/G1 stage by increasing cyclin p21 expression and inhibiting the migration and invasion abilities of HCC cells by regulating MMP2 and MMP9. The xenotransplantation studies with nude mice also showed that overexpression of α1-ACT inhibited tumourigenesis and knockdown of α1-ACT had the opposite effect. Conclusions: Our study demonstrates that α1-ACT suppresses liver cancer development and metastasis via targeting the PTEN/PI3K/AKT/mTOR signalling pathway, which may be a potential target for therapeutic intervention in HCC.

show abstract

“…Meanwhile, IL-4 serves a key role by stimulating the differentiation of naive T cells (Th0 cells) to Th2 cells (24). IL-6 is secreted by T cells and macrophages to enhance the immune reaction (25), to aid the differentiation and proliferation of T and B cells, and to advance the development of plasma cells from B cells (26). IL-10, also known as a human cytokine synthesis inhibitory factor, is an inhibitory cytokine that may hinder pathogen invasion and improve immunopathology (27).…”

Section: Discussionmentioning

confidence: 99%

Effect of Coriolus versicolor glucan on the stimulation of cytokine production in sarcoma-180-bearing mice

et al. 2017

View full text Add to dashboard Cite

Abstract. Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-α and -γ at the doses of 100 (P<0.05) and 200 (P<0.01) mg/kg, but not at 40 mg/kg (P>0.05), when compared with cyclophosphamide treatment, as a positive control. Additionally, cytokine production associated with T helper (Th)2 and Th17 cells was enhanced compared with that of Th1 cytokines, and the immunomodulatory function of CVG appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has promise in supporting cancer therapies.

show abstract

IL-6 pathway in the liver: From physiopathology to therapy

Cited by 675 publications

References 124 publications

Effects of aging on liver microcirculatory function and sinusoidal phenotype

Effects of aging on liver microcirculatory function and sinusoidal phenotype

Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN

Effect of Coriolus versicolor glucan on the stimulation of cytokine production in sarcoma-180-bearing mice

Contact Info

Product

Resources

About