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Semin Liver Dis 2019; 39(03): 275-282
DOI: 10.1055/s-0039-1685515
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Novel Drivers of the Inflammatory Response in Liver Injury and Fibrosis

Alexander Wree
1   Department of Hepatology and Gastroenterology, Charité Campus Mitte and Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
2   Department of Pediatric Gastroenterology, University of California, San Diego (UCSD), San Diego, California and Rady Children's Hospital, San Diego, California
,
Theresa Maria Holtmann
3   Department of Internal Medicine III, Aachen University Hospital, RWTH Aachen, Aachen, Germany
,
Maria Eugenia Inzaugarat
3   Department of Internal Medicine III, Aachen University Hospital, RWTH Aachen, Aachen, Germany
,
Ariel E. Feldstein
2   Department of Pediatric Gastroenterology, University of California, San Diego (UCSD), San Diego, California and Rady Children's Hospital, San Diego, California
› Author Affiliations Funding This work was funded by National Institutes of Health (NIH) grants R01 DK113592 and U01 AA024206 to A. E.F., German Research Foundation (WR173/3-1 and SFB/TRR57) to A.W., German Cancer Aid (Deutsche Krebshilfe 70113000) to A.W., and German Liver Foundation (Deutsche Leberstiftung) to T.M.H.
Further Information

Publication History

Publication Date:
17 May 2019 (online)

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Abstract

Hepatocyte demise as well as signals released by stressed hepatocytes have been now recognized as important triggers of liver inflammation. While traditional concepts classically viewed hepatocyte cell death to occur by either a nonlytic, noninflammatory form (apoptosis), or lytic, proinflammatory nonregulated cell death (necrosis), recent studies have provided evidence for additional mechanisms that can contribute to both acute and chronic liver damage. Two novel forms of cell death, pyroptosis and necroptosis, are of particular importance as they are highly regulated and intrinsically proinflammatory. Additionally, stressed hepatocytes may also release signals to attract and activate monocytes into proinflammatory macrophages. In this review, the authors discuss recent developments supporting the role of novel triggers of liver inflammation in various forms of liver injury and their potential translational implications.

Keywords

cell death - pyroptosis - necroptosis - liver injury - liver fibrosis
 

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