Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597417
2. Clinical Hepatology
Georg Thieme Verlag KG Stuttgart · New York

The regulation of inflammasome components in monocytes and macrophages from patients with decompensated cirrhosis

N Köse
1   Friedrich-Schiller University, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
,
S Stengel
1   Friedrich-Schiller University, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
,
A Steube
1   Friedrich-Schiller University, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
,
M Mai
2   Friedrich-Schiller University, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
,
A Stallmach
1   Friedrich-Schiller University, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
,
T Bruns
1   Friedrich-Schiller University, Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
› Author Affiliations
Further Information
Köse, Nilay

Publication History

Publication Date:
19 December 2016 (online)

 
 

    Background: Inflammation is a major cause of organ failure and mortality in cirrhosis and acute-on-chronic liver failure (ACLF). One major driver of inflammatory damage in a variety of liver diseases is inflammasome complexes, which control the release of pro-inflammatory cytokines and inflammatory cell death.

    Aims: This project aims on investigating regulation of inflammasome activity in cirrhosis and ACLF and its regulation by low-dose genotoxic stress.

    Methods: Circulating monocytes and peritoneal macrophages from patients with decompensation of cirrhosis, and monocytes from healthy controls were isolated and treated with different doses of low-dose epirubicin before the stimulation with inflammasome activators in vitro.

    Results: Monocytes from patients with ACLF expressed the highest levels of the inflammasome components pro-IL-1β, AIM2 and ASC as compared to monocytes and macrophages from patients without ACLF. Incubation of monocytes with serum from patients with cirrhosis as in contrast to healthy serum increased IL-1β secretion after low-dose LPS and AIM2 activation in vitro. Treatment with low-dose epirubicin prior to inflammasome activation suppressed the inflammasome-mediated IL-1β release in all investigated primary cell types as well in the monocytic cell line THP-1 in a dose-dependent fashion. The down regulation of the inflammasome activation occurred below the threshold of cytotoxicity without quantifiable DNA damage as assessed by gamma-H2AX levels.

    Conclusion: Our data suggest a regulation of the monocyte inflammasome in the context of decompensated cirrhosis and ACLF, which can be counteracted by low-dose genotoxic stress.


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    No conflict of interest has been declared by the author(s).

    Köse, Nilay