Inflammatory arthritis increases the susceptibility to acute immune-mediated hepatitis in mice through enhancing leptin expression in T cells.

Abstract

Liver function abnormalities are common in patients with inflammatory arthritis. However, the precise mechanism is still unclear. In this study, inflammatory arthritis was established in mice by subcutaneous injection of complete Freund's adjuvant, and the intravenous injection of concanavalin A (Con A) was employed to induce acute immune-mediated hepatitis in mice. The result showed that the arthritis mice were more susceptible to ConA-induced hepatitis than the control mice, as evidenced by increased hepatic necrosis, elevated serum alanine aminotransferase activity, and raised inflammatory cytokines. Besides, the in vitro assay demonstrated that the T cells from arthritis mice were more sensitive to the Con A stimulation than those from control mice. Moreover, we determined that the level of leptin, a kind of adipokine, was significantly increased in the serum and hepatic T cells of arthritis mice. Interestingly, the data indicated that the enhanced expression of leptin in hepatic T cells is responsible for the hypersensitivity of arthritis mice-derived T cells to Con A challenge. Collectively, our findings demonstrate an unexpected role of leptin in the connection between inflammatory arthritis and acute immune-mediated hepatitis, thus providing new insight into the clinical therapy of arthritis-related liver dysfunction.

• Authors: Youyi Wang, Ping Wang, Qishan Xu, Lijun Dong, Yunzhi Liu, Yu Chen, Jia Zhou, Xiao Lu, Daming Zuo, Qingyun Chen
• Journal: Molecular immunology (Mol Immunol) Vol. 140 Pg. 97-105 (12 2021) ISSN: 1872-9142 [Electronic] England
• PMID: 34673376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Cytokines
• Inflammation Mediators
• Leptin
• Concanavalin A

Topics

• Acute Disease
• Animals
• Arthritis (complications, pathology)
• Concanavalin A
• Cytokines (metabolism)
• Disease Susceptibility
• Hepatitis (complications, immunology)
• Hypersensitivity (complications, immunology)
• Inflammation (complications, pathology)
• Inflammation Mediators (metabolism)
• Leptin (metabolism)
• Liver (injuries, pathology)
• Lymphocyte Activation (immunology)
• Mice, Inbred C57BL
• Signal Transduction
• T-Lymphocytes (immunology)
• Mice