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Published on: October 21, 2017
Interleukin-24 protects against liver injury in mouse models
Hsiao-Hsuan Wang1, Jian-Hao Huang2, Min-Hao Sue2
1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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, IL-20R1-, and IL20R2-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.
Funding:
This work was supported by the Ministry of Science and Technology of Taiwan (MOST 106-2320-B-006-024) and Taiwan Liver Disease Prevention & Treatment Research Foundation.
