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
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