Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury
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. T...
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doaj-4d375793e8c847c88f1bf7109f1f52712020-12-10T00:03:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-01219379937910.3390/ijms21249379Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver InjurySha Yin0Qianwen Shi1Wenwei Shao2Chi Zhang3Yixiao Zhang4Xiaoyan Qiu5Jing Huang6Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaImmunoglobulin (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.https://www.mdpi.com/1422-0067/21/24/9379liver injuryhepatocyteIgκapoptosisConAmitochondria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sha Yin Qianwen Shi Wenwei Shao Chi Zhang Yixiao Zhang Xiaoyan Qiu Jing Huang |
spellingShingle |
Sha Yin Qianwen Shi Wenwei Shao Chi Zhang Yixiao Zhang Xiaoyan Qiu Jing Huang Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury International Journal of Molecular Sciences liver injury hepatocyte Igκ apoptosis ConA mitochondria |
author_facet |
Sha Yin Qianwen Shi Wenwei Shao Chi Zhang Yixiao Zhang Xiaoyan Qiu Jing Huang |
author_sort |
Sha Yin |
title |
Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury |
title_short |
Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury |
title_full |
Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury |
title_fullStr |
Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury |
title_full_unstemmed |
Hepatocyte-Derived Igκ Exerts a Protective Effect against ConA-Induced Acute Liver Injury |
title_sort |
hepatocyte-derived igκ exerts a protective effect against cona-induced acute liver injury |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-12-01 |
description |
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. |
topic |
liver injury hepatocyte Igκ apoptosis ConA mitochondria |
url |
https://www.mdpi.com/1422-0067/21/24/9379 |
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