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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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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. |
format | Online Article Text |
id | pubmed-7841303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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