Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury

• Main Authors: Sha Yin, Qianwen Shi, Wenwei Shao, Chi Zhang, Yixiao Zhang, Xiaoyan Qiu, Jing Huang
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: International Journal of Molecular Sciences
• Subjects: liver injury; hepatocyte; Igκ; apoptosis; ConA; mitochondria
• Online Access: https://www.mdpi.com/1422-0067/21/24/9379

Immunoglobulin (Igκ) has been reported to be expressed in sorted liver epithelial cells of μMT mice, and the sequence characteristics of hepatocyte-derived Igκ were different from those of classical B-cell-derived Igκ. However, the physiological function of hepatocyte-derived Igκ is still unclear. The expression of Igκ was firstly identified in primary hepatocytes and normal liver cell line (NCTC1469), and hepatocyte-derived Igκ expression was elevated and displayed unique localization in hepatocytes of concanavalin A (ConA)-induced hepatitis model. Moreover, <i>Igκ</i> knockout mice were more sensitive to ConA-induced hepatitis and had higher serum aspartate aminotransferase (AST) levels, more severe histological injury and a greater number of terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells as compared with littermate controls. Furthermore, knockdown of <i>Igκ</i> in primary hepatocytes and NCTC1469 cells led to accelerated activation of the mitochondrial death pathway and caspase-3 cleavage in vitro, which might be related to inhibition of NF-κB signaling pathway and activation of JNK via the cytoskeleton dynamics. Taken together, these results indicate that hepatocyte-derived Igκ mediates cellular resistance to ConA-induced liver injury by inhibiting activation of caspase-3 and the mitochondrial death pathway, suggesting that Igκ plays an important role in hepatocyte survival and exerts a protective effect against ConA-induced liver injury in mice.