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Trends Mol Med. 2018 May;24(5):458-471. doi: 10.1016/j.molmed.2018.03.005. Epub 2018 Apr 14.

IL-1 Family Cytokine Pathways Underlying NAFLD: Towards New Treatment Strategies.

Author information

1
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl-Gustav-Carus, Technische Universität Dresden, Dresden, Germany.
3
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; R&D Department, Hycult Biotech, Uden, The Netherlands. Electronic address: e.toonen@hycultbiotech.com.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Pathways responsible for the activation of IL-1 family cytokines are key in the development of NAFLD but underlying mechanisms are not fully understood. Many studies have focused on the inflammasome-caspase-1 pathway and have shown that this pathway is an important inducer of inflammation in NAFLD. However, this pathway is not solely responsible for the activation of proinflammatory cytokines. Also, neutrophil serine proteases (NSPs) are capable of activating cytokines and recent studies reported that these proteases also contribute to NAFLD. These studies provided, for the first time, evidence that this inflammasome-independent pathway is involved in NAFLD. In our opinion, these new insights open up new approaches for therapeutic intervention.

KEYWORDS:

inflammasome; inflammation; interleukin-1; neutrophil serine proteases; nonalcoholic fatty liver disease; obesity

PMID:
29665983
PMCID:
PMC5939989
[Available on 2019-05-01]
DOI:
10.1016/j.molmed.2018.03.005

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