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Inflammatory disease and cancer with a decrease in Kupffer cell numbers in Nucling‐knockout mice
Author(s) -
Sakai Takashi,
Liu Li,
Teng Xichuan,
Ishimaru Naozumi,
MukaiSakai Rika,
Tran Nam Hoang,
Kim Sun Mi,
Sano Nobuya,
Hayashi Yoshio,
Kaji Ryuji,
Fukui Kiyoshi
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24789
Subject(s) - apoptosis , knockout mouse , kupffer cell , immune system , tumor necrosis factor alpha , biology , liver cancer , cancer research , hepatitis , hepatocellular carcinoma , cancer , liver disease , immunology , endocrinology , medicine , receptor , biochemistry
Nucling is a stress‐inducible protein associated with apoptosomes. The cytochrome c‐triggered formation of apoptosomes represents a key‐initiating event in apoptosis. We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF‐κB as well. Here we show that hepatocellular carcinoma (HCC) arising spontaneously against a background of hepatitis occurred more frequently in Nucling‐knockout (KO) mice than wild‐type (WT) mice. Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling‐KO males. In the background of Nucling‐KO mice, we observed the up‐regulation of TNFα, spontaneous NF‐κB‐activation and the induction of galectin‐3 expression in liver. In addition, we observed a decrease in the number of Kupffer cells (KCs) in the KO mice. KCs are important for the hepatic immune system, acting as phagocytes or antigen‐presenting cells (APCs). We found that KCs in Nucling‐KO mice were apoptotic possibly through the up‐regulation of TNFα. These observations indicate that Nucling is important for the regulation of NF‐κB signals in liver. We propose that Nucling deficiency could be a powerful tool to reveal the NF‐κB‐related molecular networks leading to hepatitis and HCC development.