Regulation of hepatocyte fate by interferon-γ

Horras, Christopher J.; Lamb, Cheri L.; Mitchell, Kristen

doi:10.1016/j.cytogfr.2011.01.001

Cited by 93 publications

(99 citation statements)

References 150 publications

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“…In contrast, subjects with stable or slowly progressive disease not only were able to raise a timely virusspecific immune response, but also were able to maintain throughout the course of the infection higher levels of IFN-γ, a cytokine that has been shown to exert antifibrogenic effects (40). Consistent with our findings, patients with intrahepatic CD8 + T cells producing IFN-γ were reported to have less fibrosis and lower progression rates than those lacking such cells (41).…”

Section: Discussionsupporting

confidence: 82%

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

Farci

Wollenberg

Diaz

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

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Section: Discussionsupporting

confidence: 82%

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

Farci

Wollenberg

Diaz

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Reports from humans and from animal models suggest that IFNg controls infections through viral clearance and limiting virus replication (Costa et al, 2012;Horras et al, 2011;Pal et al, 2014;Shresta et al, 2004). Notably, dengue viral titres correlate with disease severity (Endy et al, 2004;Vaughn et al, 2000), but are plausibly influenced by DENV type and infection status (Duyen et al, 2011).…”

mentioning

confidence: 99%

Markers of dengue severity: a systematic review of cytokines and chemokines

Lee

Leong

Wilder‐Smith

2016

Journal of General Virology

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The prognosis of dengue remains a challenge in the early, objective triage of patients with dengue fever of differing severity. Circulating immuno-modulating proteins have brought new possibilities as prognostic markers of severe dengue (SD). This systematic review is devoted to understanding the potential utility of blood-based cytokines and chemokines as prognostication markers of SD based on the current literature. PubMed and Embase were searched. Of 794 candidate articles, 685 abstracts were screened against our exclusion/inclusion criteria and 25 (3.6 %) studies met the quality assessments. A total of 18 studies were retrospective observational and 2 were prospective cohort studies. Elevated IL-10, up to day 7 of fever onset, stood out as a candidate prognostic marker for SD using the 1997 and 2009 World Health Organization (WHO) case definitions. IFNg was another potential prognostic marker of SD (1997 WHO case definition), but its levels varied between studies. Significant heterogeneity in methodologies and patient cohorts prevent ready application of IL-10 and IFNg as prognostic markers to other dengue populations. Our results suggest that the current non-randomized studies are delivering inconsistent messages and higher-quality studies, with consistent methodologies and validation in independent patient cohorts, are needed to delineate confounding variables. Major gaps identified were full accounting and transparency of sampling days, dengue virus type, infection status and age group.

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“…Indeed, the secretome of ADSCs has been shown to possess the capability of immunomodulation [19]. It is well known that IL-6, IDO, IFNγ and TNF-α are modulators of the hepatocyte immune response and regeneration [20][21][22][23]. We examined production of the four cytokines in the supernatant and found a high level of IL-6 in the coculture medium, while in the rat hepatocyte monoculture, IL-6 concentration was too low to be measured by ELISA.…”

Section: Discussionmentioning

confidence: 99%

Maintenance of rat hepatocytes under inflammation by coculture with human orbital fat-derived stem cells

Chen¹,

Zhang

Liu

et al. 2012

Cellular and Molecular Biology Letters

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Abbreviations used: ALF -acute liver failure; ADSCs -adipose tissue-derived stem cells; ALB -albumin; CK32 -connexin 32; CYP3A4 -cytochrome P450 subtype 3A4; IDOindoleamine 2,3-dioxygenase; IFN -interferon; IL -interleukin; GAPDH -glyceraldehyde-3-phosphate dehydrogenase; MSCs -mesenchymal stem cells; OFSCs -orbital fat-derived stem cells; PAS -periodic acid-Schiff; TDO2 -tryptophan 2,3-dioxygenase; TNF -tumor necrotic factor Abstract: Preservation of hepatocyte functions in vitro will undoubtedly help the management of acute liver failure. The coculture system may be able to prevent functional decline of hepatocytes. It has already been shown that hepatocytes, when cocultured with bone marrow mesenchymal stem cells, could undergo long-term culture in vitro without loss of functions. In this study, human orbital fat-derived stem cells were isolated and cocultured with rat hepatocytes. When treated with serum from an acute liver failure patient, rat hepatocyte monoculture showed reduction of cell viability and loss of liverspecific functions. However, rat hepatocytes in the coculture system were still able to secret albumin and synthesize urea. IL-6 was significantly elevated in the coculture of rat hepatocyte with orbital fat-derived stem cells, and it might be the key immunoregulator which protects rat hepatocytes against inflammation. Our data confirmed that orbital fat-derived stem cells, or other adipose tissue-derived stem cells, are an ideal candidate to support rat hepatocyte functions in vitro.

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Regulation of hepatocyte fate by interferon-γ

Cited by 93 publications

References 150 publications

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

Markers of dengue severity: a systematic review of cytokines and chemokines

Maintenance of rat hepatocytes under inflammation by coculture with human orbital fat-derived stem cells

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