Journal
EBIOMEDICINE
Volume 64, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2021.103213
Keywords
Interleukin-24; Liver fibrosis; Thioacetamide-induced liver injury; Hepatic stellate cells
Funding
- Laboratory Animal Center, College of Medicine, National Cheng Kung University
- Ministry of Science and Technology of Taiwan [MOST 106-2320-B-006-024]
- Taiwan Liver Disease Prevention & Treatment Research Foundation
- Core Facility of Taiwan Mouse Clinic and Animal Consortium
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IL-24 plays a key protective role in liver injury progression by protecting hepatocytes and preventing liver fibrosis through inhibiting HSC activation. The protective role of IL-24 is mainly independent of IL-20R1.
Background: Interleukin-24 (IL-24) binds to two kinds of receptor complexes, namely IL-20R1/IL-20R2 and IL-20R2/IL-22R1, which are also bound by IL-20. IL-20 plays a detrimental role in liver fibrosis. Due to the sharing of receptor complexes, we aimed to determine whether IL-24 also participates in liver fibrosis. Methods: Clinical biopsy specimens from various stages of liver fibrosis were used to analyze IL-24 expression. IL-24 protein was administered to mice with thioacetamide (TAA)-induced liver injury. The direct effects of IL-24 on mouse primary hepatocytes or hepatic stellate cells (HSCs) were analyzed. Wild-type, IL20R1-, and IL-20R2-deficient mice were used to establish a model of acute TAA-induced liver injury. Findings: Among patients with more severe liver fibrosis, there was a reduced IL-24/IL-20 ratio. Administration of IL-24 protein protected mice from TAA-induced liver injury and reduction of liver inflammation by antioxidant effects. IL-24 protected hepatocytes from TAA-induced apoptosis and prevented liver fibrosis through the inhibition of the HSCs activation. The protective role of IL-24 acted on liver cells were mainly IL-20R1-independent. IL-20R2-deficient mice exhibited more severe liver injury upon TAA treatment, thus confirming the protective role of IL-24. Interpretation: IL-24 plays a key protective role in the progression of liver injury and has therapeutic potential for treating liver injuries. (C) 2021 The Authors. Published by Elsevier B.V.
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