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Interleukin-24 protects against liver injury in mouse models

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...

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Autores principales: Wang, Hsiao-Hsuan, Huang, Jian-Hao, Sue, Min-Hao, Ho, Wei-Chih, Hsu, Yu-Hsiang, Chang, Kung-Chao, Chang, Ming-Shi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841303/
https://www.ncbi.nlm.nih.gov/pubmed/33508745
http://dx.doi.org/10.1016/j.ebiom.2021.103213
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author Wang, Hsiao-Hsuan
Huang, Jian-Hao
Sue, Min-Hao
Ho, Wei-Chih
Hsu, Yu-Hsiang
Chang, Kung-Chao
Chang, Ming-Shi
author_facet Wang, Hsiao-Hsuan
Huang, Jian-Hao
Sue, Min-Hao
Ho, Wei-Chih
Hsu, Yu-Hsiang
Chang, Kung-Chao
Chang, Ming-Shi
author_sort Wang, Hsiao-Hsuan
collection PubMed
description 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.
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spelling pubmed-78413032021-02-02 Interleukin-24 protects against liver injury in mouse models Wang, Hsiao-Hsuan Huang, Jian-Hao Sue, Min-Hao Ho, Wei-Chih Hsu, Yu-Hsiang Chang, Kung-Chao Chang, Ming-Shi EBioMedicine Research Paper 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. Elsevier 2021-01-25 /pmc/articles/PMC7841303/ /pubmed/33508745 http://dx.doi.org/10.1016/j.ebiom.2021.103213 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Wang, Hsiao-Hsuan
Huang, Jian-Hao
Sue, Min-Hao
Ho, Wei-Chih
Hsu, Yu-Hsiang
Chang, Kung-Chao
Chang, Ming-Shi
Interleukin-24 protects against liver injury in mouse models
title Interleukin-24 protects against liver injury in mouse models
title_full Interleukin-24 protects against liver injury in mouse models
title_fullStr Interleukin-24 protects against liver injury in mouse models
title_full_unstemmed Interleukin-24 protects against liver injury in mouse models
title_short Interleukin-24 protects against liver injury in mouse models
title_sort interleukin-24 protects against liver injury in mouse models
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841303/
https://www.ncbi.nlm.nih.gov/pubmed/33508745
http://dx.doi.org/10.1016/j.ebiom.2021.103213
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