Fatty acid binding protein 7 regulates phagocytosis and cytokine production in Kupffer cells during liver injury

Hirofumi Miyazaki; Tomoo Sawada; Miwa Kiyohira; Zhiqian Yu; Keiji Nakamura; Yuki Yasumoto; Yoshiteru Kagawa; Majid Ebrahimi; Ariful Islam; Kazem Sharifi; Saki Kawamura; Takanori Kodama; Yui Yamamoto; Yasuhiro Adachi; Nobuko Tokuda; Shuji Terai; Isao Sakaida; Toshizo Ishikawa; Yuji Owada

doi:10.1016/j.ajpath.2014.05.015

Fatty acid binding protein 7 regulates phagocytosis and cytokine production in Kupffer cells during liver injury

Am J Pathol. 2014 Sep;184(9):2505-15. doi: 10.1016/j.ajpath.2014.05.015. Epub 2014 Jul 18.

Authors

Hirofumi Miyazaki¹, Tomoo Sawada¹, Miwa Kiyohira¹, Zhiqian Yu², Keiji Nakamura¹, Yuki Yasumoto¹, Yoshiteru Kagawa¹, Majid Ebrahimi¹, Ariful Islam¹, Kazem Sharifi¹, Saki Kawamura¹, Takanori Kodama¹, Yui Yamamoto¹, Yasuhiro Adachi³, Nobuko Tokuda⁴, Shuji Terai⁵, Isao Sakaida⁵, Toshizo Ishikawa⁶, Yuji Owada⁷

Affiliations

¹ Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
² Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan.
³ Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁴ Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan; Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁵ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
⁶ Division of Neurosciences, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
⁷ Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube, Japan. Electronic address: yowada@yamaguchi-u.ac.jp.

PMID: 25041855
DOI: 10.1016/j.ajpath.2014.05.015

Abstract

Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-α, monocyte chemoattractant protein-1, and transforming growth factor-β) was decreased in the liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Carbon Tetrachloride / toxicity
Chemical and Drug Induced Liver Injury / metabolism
Chemical and Drug Induced Liver Injury / pathology*
Cytokines / biosynthesis*
Enzyme-Linked Immunosorbent Assay
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins / metabolism*
Flow Cytometry
Fluorescent Antibody Technique
Immunohistochemistry
In Situ Nick-End Labeling
Kupffer Cells / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins / metabolism*
Phagocytosis / physiology*
Reverse Transcriptase Polymerase Chain Reaction

Substances

Cytokines
Fabp7 protein, mouse
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins
Nerve Tissue Proteins
Carbon Tetrachloride