Liver Failure Impairs the Intrahepatic Elimination of Interleukin-6, Tumor Necrosis Factor-Alpha, Hepatocyte Growth Factor, and Transforming Growth Factor-Beta

Porowski, D; Wirkowska, Agnieszka; Hryniewiecka, Ewa; Wyzgał, Janusz; Pacholczyk, Marek; Pączek, Leszek

doi:10.1155/2015/934065

Cited by 24 publications

(19 citation statements)

References 37 publications

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“…However, few studies investigated the effect of TPE and DPMAS on serum levels of IL‐6 in ACLF patients. Our results showed that serum IL‐6 was consistently increased after both TPE and DPMAS, which may be due to increased production and impaired elimination rates of IL‐6 in HBV‐ACLF patients, higher than removal rates by TPE and DPMAS.…”

Section: Discussionmentioning

confidence: 65%

Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus‐infected acute‐on‐chronic liver failure treated by entercavir: A prospective study

Wan

et al. 2017

J of Clinical Apheresis

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Section: Discussionmentioning

confidence: 65%

Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus‐infected acute‐on‐chronic liver failure treated by entercavir: A prospective study

Wan

et al. 2017

J of Clinical Apheresis

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“…TGFβ1 possesses a wide range of biological functions, such as suppression of the proliferation of gingival epithelial cells (29,30), early embryogenesis (31) and hematopoiesis (32), apoptosis of gingival epithelial cells, and formation of the junctional epithelium (33). Apoptosis can occur through three major pathways: the mitochondrial pathway, the Fas cell surface receptor pathway, and endoplasmic reticulum stress (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

TGFβ1-induced Amelotin gene expression is downregulated by Bax expression in mouse gingival epithelial cells

et al. 2018

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Amelotin (AMTN) is induced upon initiation of apoptosis by transforming growth factor beta1 (TGFβ1) and is mediated by Smad3 in gingival epithelial cells (GE1 cells). This upregulation of AMTN gene expression is temporary, and the mechanism responsible is still unclear. The present study investigated the transcriptional downregulation of TGFβ1-induced AMTN gene expression in GE1 cells during the progression of apoptosis. To examine time-dependent changes in the levels of AMTN, Smad3 and Bax mRNA induced by TGFβ1, real-time PCR analyses were performed. Immunocytochemistry was carried out to detect the expression of Smad3 and Bax. Transient transfection analyses were performed using mouse AMTN gene promoter constructs of various lengths including Smad response elements (SBEs), in the presence or absence of TGFβ1. Changes in Smad3 binding to SBEs resulting from overexpression of Bax were examined using ChIP assays. Overexpression of Bax dramatically downregulated the levels of TGFβ1-induced AMTN mRNA and transcription of the AMTN gene. Smad3 binding to SBEs in the mouse AMTN gene promoter was induced by overexpression of Smad3 or TGFβ1, and this was inhibited by Bax overexpression. These results show that the levels of AMTN mRNA induced by TGFβ1 and Smad3 are decreased by robust expression of Bax in gingival epithelial cells.

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“…Importantly, in our experimental setup we used TNF concentrations that can be detected in different areas of the liver vasculature network (3–10 ng/ml) under physiological and pathological conditions (Porowski et al, 2015 ). However, under some conditions, such as non-alcoholic steatohepatitis (NASH) or after liver transplantation much higher TNF levels may be measurable (34.2 and 43 ng/ml, respectively).…”

Section: Discussionmentioning

confidence: 99%

A20/TNFAIP3 Discriminates Tumor Necrosis Factor (TNF)-Induced NF-κB from JNK Pathway Activation in Hepatocytes

et al. 2017

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In the liver tumor necrosis factor (TNF)-induced signaling critically regulates the immune response of non-parenchymal cells as well as proliferation and apoptosis of hepatocytes via activation of the NF-κB and JNK pathways. Especially, the induction of negative feedback regulators, such as IκBα and A20 is responsible for the dynamic and time-restricted response of these important pathways. However, the precise mechanisms responsible for different TNF-induced phenotypes under physiological stimulation conditions are not completely understood so far. In addition, it is not known if varying TNF concentrations may differentially affect the desensitization properties of both pathways. By using computational modeling, we first showed that TNF-induced activation and downstream signaling is qualitatively comparable between primary mouse hepatocytes and immortalized hepatocellular carcinoma (HCC) cells. In order to define physiologically relevant TNF levels, which allow for an adjustable and dynamic NF-κB/JNK pathway response in parenchymal liver cells, a range of cytokine concentrations was defined that led to gradual pathway responses in HCC cells (1–5 ng/ml). Repeated stimulations with low (1 ng/ml), medium (2.5 ng/ml) and high (5 ng/ml) TNF amounts demonstrated that JNK signaling was still active at cytokine concentrations, which led to dampened NF-κB signaling illustrating differential pathway responsiveness depending on TNF input dynamics. SiRNA-mediated inhibition of the negative feedback regulator A20 (syn. TNFAIP3) or its overexpression did not significantly affect the NF-κB response. In contrast, A20 silencing increased the JNK response, while its overexpression dampened JNK phosphorylation. In addition, the A20 knockdown sensitized hepatocellular cells to TNF-induced cleavage and activity of the effector caspase-3. In conclusion, a mathematical model-based approach shows that the TNF-induced pathway responses are qualitatively comparable in primary and immortalized mouse hepatocytes. The cytokine amount defines the pathway responsiveness under repeated treatment conditions with NF-κB signaling being dampened ‘earlier’ than JNK. A20 appears to be the molecular switch discriminating between NF-κB and JNK signaling when stimulating with varying physiological cytokine concentrations.

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Liver Failure Impairs the Intrahepatic Elimination of Interleukin-6, Tumor Necrosis Factor-Alpha, Hepatocyte Growth Factor, and Transforming Growth Factor-Beta

Cited by 24 publications

References 37 publications

Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus‐infected acute‐on‐chronic liver failure treated by entercavir: A prospective study

Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus‐infected acute‐on‐chronic liver failure treated by entercavir: A prospective study

TGFβ1-induced Amelotin gene expression is downregulated by Bax expression in mouse gingival epithelial cells

A20/TNFAIP3 Discriminates Tumor Necrosis Factor (TNF)-Induced NF-κB from JNK Pathway Activation in Hepatocytes

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