Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice

Sultan, Maya; Ben‐Ari, Ziv; Masoud, Rula; Pappo, Orit; Harats, Dror; Kamari, Yehuda; Safran, Michal

doi:10.1371/journal.pone.0184084

Cited by 39 publications

(42 citation statements)

References 41 publications

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“…It would be informative to reveal that patients who received SOT in the end stage organ disease state have higher HCMV IgG seropositive rates and titres compared to heathy individuals. This finding might be associated with asymptomatic intermittent HCMV replication and immune boosting against HCMV in chronic end stage medical diseases as well as polyclonal immune activation through proinflammatory cytokine release upon fulminant acute organ failure leading to SOT [37][38][39][40].…”

Section: Discussionmentioning

confidence: 98%

Human Cytomegalovirus Seroprevalence and Titres in Solid Organ Transplant Recipients and Transplant Donors in Seoul, South Korea

Kwon

Yoo

et al. 2019

Preprint

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Background: Human cytomegalovirus (HCMV) can cause poor outcomes in solid organ transplant (SOT) recipients; moreover, it is associated with cardiovascular diseases (CVD) in the general population. Accordingly, anti-HCMV immunoglobulin G (IgG) seroepidemiology may be useful in identifying the risk of post-SOT HCMV infection or disease as well as immunosenescence or CVD. However, HCMV seroprevalence and titre have not been fully evaluated with regard to age distribution or compared between SOT recipients and healthy individuals in South Korea. Methods: We retrospectively retrieved all unduplicated anti-HCMV IgG results of individuals aged > 1 year evaluated between July 2006 and November 2017 at Severance Hospital in Seoul. The cohort, excluding haematopoietic stem cell transplant recipients and subjects with equivocal values, included 2184 SOT recipients and 3015 healthy transplant donors. All IgG results in the SOT recipients were measured during the pre-transplant period. Results: The overall IgG seroprevalence and titres were significantly higher among SOT recipients than among healthy donors (98.7% vs. 88.6%, p < 0.001, and 64.7 ± 44.3 vs. 49.8 ± 20.6 arbitrary units/mL, p < 0.001, respectively). The lowest seropositive rate in the SOT group was observed in recipients aged between 11 and 15 years (70.6%). The frequency of seropositivity among adults aged ≥ 41 years increased to ≥ 90% in SOT recipients and healthy donors. Age was independently associated with higher HCMV seroprevalence (41–60 years, OR, 76.4, 95% CI, 24.5–238.9, p < 0.001; ≥ 61 years, OR, 4.4, 95% CI, 1.3–14.9, p < 0.001, compared to ≤ 40 years). The healthy donor group had an independently low HCMV seropositive rate (OR, 0.1, 95% CI, 0.1–0.2, p < 0.001). Conclusions: HCMV seropositivity was the lowest among school-aged children and adolescents. IgG testing revealed an intermediate serostatus risk of post-transplant HCMV infection and disease for most adult SOT recipients in South Korea.

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Section: Discussionmentioning

confidence: 98%

Human Cytomegalovirus Seroprevalence and Titres in Solid Organ Transplant Recipients and Transplant Donors in Seoul, South Korea

Kwon

Yoo

et al. 2019

Preprint

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“…As a fatal complication of acute hepatic injury, FHF occurs unpredictably and is marked by the unexpected onset of hepatic encephalopathy and impaired hepatic function 28 . Interestingly, various lncRNAs, such as H19, HOTAIR, and MALAT-1, and their association with liver diseases have been highlighted as potential markers for disease progression or prognosis 29 .…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation

et al. 2020

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Fulminant hepatic failure (FHF) refers to the rapid development of severe acute liver injury with impaired synthetic function and encephalopathy in people with normal liver or well-compensated liver disease. This study aimed to investigate the function of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) on the proliferation and apoptosis of hepatocytes in FHF. Our results revealed that lncRNA NEAT1 was upregulated in cell and animal models of FHF induced by D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Overexpression of lncRNA NEAT1 resulted in elevated hepatocyte apoptosis and impaired large tumor-suppressor kinase 2 (LATS2) expression and proliferation. Functional analysis revealed that knockdown of lncRNA NEAT1 inhibited hepatocyte apoptosis and induced proliferation both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression. Furthermore, ectopic expression of LATS2 increased proliferation and inhibited hepatocyte apoptosis by regulating the Hippo/Yes-associated protein (YAP) signaling pathway. Taken together, our findings indicate that lncRNA NEAT1 might serve as a novel target for FHF therapy due to its regulation of H3K27me3 methylation-dependent promotion of LATS2.

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“…In this model, LPS induced TNFα production by Kupffer cells (KCs) is demonstrated to play critical roles in the etiopathogenesis of ALF [25][26][27][28]. In addition, several studies showed that IL1β also contributes to the ampli cation of hepatocytes death and hepatic in ammation [29,30]. However, type I IL-1R knockout mice showed no difference in sensitivity to the challenge of DGalN plus LPS [31].…”

Section: Introductionmentioning

confidence: 99%

NLRP3 is dispensable for D-galactosamine/Lipopolysaccharide-induced fulminant hepatitis

Zhang

Tao

Wang

et al. 2020

Preprint

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Background: The NOD-like receptor family protein 3 (NLRP3) inflammasome is involved in the progression of liver inflammation. NLRP3 inactivation has been shown to protect mice against multiple types of experimental liver injury. However, it is unclear whether NLRP3 contributes to D-Galactosamine (DGalN) plus lipopolysaccharide (LPS) induced fatal hepatitis. This study aims to examine the function of NLRP3 inflammasome in DGalN/LPS induced acute liver failure.Method: The expression of inflammasomes was detected by quantitative PCR. Wild type (WT) mice and NLRP3 knockout mice were given an intraperitoneal injection of DGalN plus LPS. Liver damage was examined at 6 h post DGalN/LPS administration by histological analysis and serum aminotransferases measurement. Hepatocyte apoptosis and pyroptosis was detected with TUNEL assay, immunohistochemistry (IHC) staining, and western blot. Hepatic macrophages (F4/80+) and neutrophils (Ly6G+) were analyzed by IHC staining. The proinflammatory cytokines levels in serum and liver were examined using cytometric bead array and quantitative PCR. Hepatic IL1β level was further detected by western blot.Result: The hepatic NLRP3 activity was upregulated in WT mice treated with DGalN/LPS. Nlrp3−/− and WT mice showed similar mortality against lethal dose of DGalN/LPS. Serum aminotransferases levels and liver necrosis area of Nlrp3−/− mice did not differ from that in WT mice after DGalN/LPS injection. The numbers of liver TUNEL positive cells and cleaved caspase3 positive hepatocytes were comparable between Nlrp3−/− and WT mice. The hepatic GSDMDNterm peptide production also showed no difference between Nlrp3−/− and WT mice. Mice treated with DGalN/LPS displayed significantly increased numbers of intrahepatic F4/80+ cells and Ly6G+ cells, but the cell numbers in Nlrp3−/− mice livers were similar to those in WT mice. Consistently, serum and hepatic TNFα, IL6, and MCP-1 levels were similar between Nlrp3−/− and WT mice upon DGalN/LPS administration, but serum IL1β and hepatic mature IL1β level in Nlrp3−/− mice was reduced.Conclusions: NLRP3 ablation does not protect mice from DGalN/LPS induced acute liver failure, nor affect hepatocyte apoptosis and pyroptosis. Deficiency of NLRP3 has a limited effect on intrahepatic inflammatory response induced by DGalN/LPS treatment. NLRP3 inflammasome does not appear to be a major contributor to DGalN/LPS induced fatal hepatitis.

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Interleukin-1α and Interleukin-1β play a central role in the pathogenesis of fulminant hepatic failure in mice

Cited by 39 publications

References 41 publications

Human Cytomegalovirus Seroprevalence and Titres in Solid Organ Transplant Recipients and Transplant Donors in Seoul, South Korea

Human Cytomegalovirus Seroprevalence and Titres in Solid Organ Transplant Recipients and Transplant Donors in Seoul, South Korea

Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation

NLRP3 is dispensable for D-galactosamine/Lipopolysaccharide-induced fulminant hepatitis

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