Inflammasome activation in the liver: Focus on alcoholic and non-alcoholic steatohepatitis

Szabó, Gyöngyi; Iracheta-Vellve, Arvin

doi:10.1016/j.clinre.2015.06.012

Cited by 35 publications

(23 citation statements)

References 45 publications

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“…The inflammasome consists of an intracellular multi-protein complex that is formed upon exposure of a wide range of stimuli generated during liver injury and sterile inflammation 35 . The nucleotide oligomerization domain (NOD)-like receptors (NLRs), that belong to the pattern recognition receptors family, recognize damage associated molecular patterns (DAMPs) and pathogen associated molecular patterns (PAMPs) signals and promotes the assembly of inflammasome proteins 21 .…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Cabrera

Wree

Povero

et al. 2017

Sci Rep

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Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid–defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week). Also, we assessed serum levels of alanine-aminotransferase (ALT), liver histology, hepatic triglyceride content (HTC) and hepatic expression of pro-inflammatory, pro-fibrotic and inflammasome genes. Inflammasome activation was also evaluated in fat-laden HepG2 cells. Our results showed that ANDRO administration decreased HTC and attenuated hepatic inflammation and fibrosis in CDAA-fed mice. ANDRO treatment determined a strong reduction in hepatic macrophage infiltration and reduced hepatic mRNA levels of both pro-inflammatory and pro-fibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1β expression through NF-κB inhibition in fat-laden HepG2 cells and inflammasome disassembly. In conclusion, ANDRO administration reduces inflammation and fibrosis in experimental NASH. Inflammasome modulation by a NF-κB-dependent mechanism may be involved in the therapeutic effects of ANDRO.

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Section: Discussionmentioning

confidence: 99%

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Cabrera

Wree

Povero

et al. 2017

Sci Rep

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“…damage associated molecular patterns (DAMPs)), and the activation of their cognate sensors or pattern recognition receptors that are responsible for the downstream signaling cascade of the inflammasome. The role of the inflammasome in NASH has recently been reviewed [18]. Briefly, the inflammasome is comprised of the receptors of the danger signals including toll-like receptors (TLRs) and nucleotide-binding oglimerization domain (NOD)-like receptors (NLRs), the adaptor protein apoptosis-associated speclike protein (ASC), and the effector molecule caspase-1.…”

Section: Nash and Liver Inflammationmentioning

confidence: 99%

Role of FXR in Liver Inflammation During Nonalcoholic Steatohepatitis

Armstrong

Guo

2017

Curr Pharmacol Rep

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Purpose of review About 15–25% of patients with simple steatosis of non-alcoholic fatty liver disease progresses to non-alcoholic steatohepatitis (NASH), and the underlying mechanism for this progression has not been elucidated. NASH ultimately could progress to cirrhosis, an irreversible condition. Recent findings Farnesoid X receptor (FXR) has been studied for its role in modulating inflammation, and the expression of FXR is down-regulated during NASH development. FXR deficiency has shown to progress and exacerbate NASH development, and FXR activation has been protective against liver inflammation associated with NASH. The expression of factors in both the adaptive and innate immune response in the liver are regulated in a FXR-dependent and -independent manner. Summary Therefore, understanding key signaling pathways of liver inflammation in NASH is important to determine essential components that predispose, progress, or exacerbate NASH. FXR has been identified as a therapeutic target for NASH to prevent liver inflammation.

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“…Recently, it has been shown by various groups that P2X7 receptor‐activated NLRP3 inflammasome signalling in neutrophils results in release IL‐1 β and IL‐18, but not IL‐1α and IL‐33, and it relies on the same receptors and inflammasome sensor that have been shown to play important roles in mouse models of ALD (reviewed in Ref. ). The decreased MPO staining in Anakinra‐treated mice suggests an IL‐1 feedforward loop resulting in neutrophil recruitment to the liver.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice

Iracheta-Vellve

Petrášek

Gyogyosi

et al. 2017

Liver International

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Background & Aims Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown. Methods Here we tested IL-1 receptor antagonist to block IL-1 signaling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH. Results We observed that inhibition of IL-1 signaling decreased liver inflammation, neutrophil infiltration, enhanced regeneration of hepatocytes, and resulted in increased rate of recovery from liver injury in AH. Conclusion Our novel findings suggest that IL-1 drives sustained liver inflammation and impaired hepatocyte regeneration even after cessation of ethanol exposure.

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Inflammasome activation in the liver: Focus on alcoholic and non-alcoholic steatohepatitis

Cited by 35 publications

References 45 publications

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Role of FXR in Liver Inflammation During Nonalcoholic Steatohepatitis

Interleukin‐1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice

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