Interleukin 28A aggravates Con A‐induced acute liver injury by promoting the recruitment of M1 macrophages

Author:

Zhang Junfeng12,Cheng Dalei13,Zhang Hui12,Liu Zhihong4,Gao Min5,Wei Li6,Yan Fenglian12,Li Chunxia12,Wang Lin7,Dong Guanjun12,Wang Changying12,Zhao Mingsheng12,Zhu Yuanbo12,Xiong Huabao1ORCID

Affiliation:

1. Institute of Immunology and Molecular Medicine Jining Medical University Jining China

2. Jining Key Laboratory of Immunology Jining Medical University Jining China

3. School of Basic Medical Sciences Anhui Medical University Hefei Anhui China

4. School of Basic Medicine Shandong First Medical University Jinan China

5. Clinical Laboratory Jining First People's Hospital Jining China

6. Affiliated Hospital of Jining Medical University Jining Medical University Jining China

7. Cheeloo College of Medicine Shandong University Jinan Shandong China

Abstract

AbstractImmune‐mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin‐28A (IL‐28A), a member of the IL‐10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL‐28A, its role in immune‐mediated acute injury remains unclear. The present study investigated the role of IL‐28A in concanavalin A (Con A)‐induced acute immune liver injury. After Con A injection in mice, IL‐28A level significantly increased. IL‐28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL‐28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL‐28A‐deficiency group than in the wild‐type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL‐28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), IL‐12, IL‐6, and IL‐1β, by M1 macrophages decreased significantly in the IL‐28A‐deficiency group. Western blotting demonstrated that IL‐28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)‐κB, mitogen‐activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL‐28A deletion plays an important protective role in the Con A‐induced acute liver injury model and IL‐28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF‐κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune‐related hepatic injury.

Funder

Natural Science Foundation of Shandong Province

National Natural Science Foundation of China

Publisher

Wiley

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1. The Role of Interferon Regulatory Factors in Liver Diseases;International Journal of Molecular Sciences;2024-06-22

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