Frontline Science: Concanavalin A-induced acute hepatitis is attenuated in vitamin D receptor knockout mice with decreased immune cell function
Autor: | Naoki Umeda, Makoto Makishima, Hiroyuki Nakashima, Kaori Endo-Umeda, Shuhji Seki, Shigeaki Kato |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Kupffer Cells medicine.medical_treatment Immunology Calcitriol receptor Peripheral blood mononuclear cell Hepatitis 03 medical and health sciences 0302 clinical medicine Immune system Phagocytosis Internal medicine Concanavalin A polycyclic compounds medicine Animals Immunology and Allergy RNA Messenger Inflammation Mice Knockout Innate immune system biology digestive oral and skin physiology NADPH Oxidases Cell Biology medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology Cytokine Gene Expression Regulation Liver 030220 oncology & carcinogenesis Acute Disease Knockout mouse Leukocytes Mononuclear biology.protein Cytokines Receptors Calcitriol lipids (amino acids peptides and proteins) Inflammation Mediators Reactive Oxygen Species |
Zdroj: | Journal of Leukocyte Biology. 106:791-801 |
ISSN: | 1938-3673 0741-5400 |
DOI: | 10.1002/jlb.3hi0219-048r |
Popis: | The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D, 1α,25-dihydroxyvitamin D3, and regulates various physiologic processes, such as bone and calcium metabolism, cellular proliferation and differentiation, and immunity. VDR is highly expressed in the intestine, kidney, bone, and macrophages, but is expressed at a low level in the liver. The liver is a major metabolic organ and also acts as an immune gateway for dietary nutrients and xenobiotics. In this study, we investigated the function of VDR in hepatic immune cells, such as Kupffer cells/macrophages, utilizing VDR knockout (KO) mice. We showed that VDR is functionally expressed in hepatic mononuclear cells, specifically resident Kupffer cells. We examined the role of VDR in acute hepatitis induced by concanavalin A (Con-A) and found that Con-A-induced hepatitis is attenuated in VDR-KO mice compared to wild-type (WT) mice. Con-A-induced hepatitis is known to be mediated by NKT cell activation, cytokine production, and reactive oxygen species (ROS) production in Kupffer cells/macrophages. However, the proportions of Kupffer cells/macrophages and the NKT cell activation were similar in the liver of WT and VDR-KO mice and inflammatory cytokine gene expression was increased in VDR-KO mice. On the other hand, plasma and hepatic ROS levels were decreased in the liver of VDR-KO mice compared to WT mice. The phagocytic activity of resident Kupffer cells and hepatic neutrophils were also decreased in VDR-KO mice. Therefore, VDR is necessary for Con-A-induced acute hepatitis and plays an important role in hepatic immune cell functions. |
Databáze: | OpenAIRE |
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