Hepatocyte-Derived Ig Kappa Exerts A Protective Effect Against Cona-Induced Acute Liver Injury

Immunoglobulin (Ig kappa) has been reported to be expressed in sorted liver epithelial cells of mu MT mice, and the sequence characteristics of hepatocyte-derived Ig kappa were different from those of classical B-cell-derived Ig kappa. However, the physiological function of hepatocyte-derived Ig kappa is still unclear. The expression of Ig kappa was firstly identified in primary hepatocytes and normal liver cell line (NCTC1469), and hepatocyte-derived Ig kappa expression was elevated and displayed unique localization in hepatocytes of concanavalin A (ConA)-induced hepatitis model. Moreover, Ig kappa 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 Ig kappa 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-kappa B signaling pathway and activation of JNK via the cytoskeleton dynamics. Taken together, these results indicate that hepatocyte-derived Ig kappa mediates cellular resistance to ConA-induced liver injury by inhibiting activation of caspase-3 and the mitochondrial death pathway, suggesting that Ig kappa plays an important role in hepatocyte survival and exerts a protective effect against ConA-induced liver injury in mice.