2. Academic Validation
  3. Alleviation of lipopolysaccharide/d-galactosamine-induced liver injury in leukocyte cell-derived chemotaxin 2 deficient mice

Alleviation of lipopolysaccharide/d-galactosamine-induced liver injury in leukocyte cell-derived chemotaxin 2 deficient mice

  • Biochem Biophys Rep. 2017 Oct 13;12:166-171. doi: 10.1016/j.bbrep.2017.09.011.
Akinori Okumura 1,  Takeshi Saito 2,  Minoru Tobiume 3,  Yuki Hashimoto 4,  Yuko Sato 3,  Takashi Umeyama 4,  Minoru Nagi 4,  Koichi Tanabe 5,  Hiroyuki Unoki-Kubota 1,  Yasushi Kaburagi 1,  Hideki Hasegawa 3,  Yoshitsugu Miyazaki 4,  Satoshi Yamagoe 4
Affiliations

Affiliations

  • 1 Department of Diabetic Complications, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
  • 2 NARO Western Region Agricultural Research Center, 1-3-1 Senyu-cho, Zentsuji, Kagawa 765-8508, Japan.
  • 3 Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
  • 4 Department of Chemotherapy and Mycosis, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
  • 5 Department of Food Science and Human Nutrition, Faculty of Agriculture, Ryukoku University, 1-5 Yokotani, Seta Oe-cho, Otsu, Shiga 520-2194, Japan.
PMID: 29090278 DOI: 10.1016/j.bbrep.2017.09.011
Abstract

Leukocyte cell-derived chemotaxin 2 (LECT2) is a secreted pleiotropic protein that is mainly produced by the liver. We have previously shown that LECT2 plays an important role in the pathogenesis of inflammatory liver diseases. Lipopolysaccharide/d-galactosamine (LPS/d-GalN)-induced acute liver injury is a known animal model of fulminant hepatic failure. Here we found that this hepatic injury was alleviated in LECT2-deficient mice. The levels of TNF-α and IFN-γ, which mediate this hepatitis, had significantly decreased in these mice, with the decrease in IFN-γ production notably greater than that in TNF-α. We therefore analyzed IFN-γ-producing cells in liver mononuclear cells. Flow cytometric analysis showed significantly reduced IFN-γ production in hepatic NK and NKT cells in LECT2-deficient mice compared with in wild-type mice. We also demonstrated a decrease in IFN-γ production in LECT2-deficient mice after systemic administration of recombinant IL-12, which is known to induce IFN-γ in NK and NKT cells. These results indicate that a decrease of IFN-γ production in NK and NKT cells was involved in the alleviation of LPS/d-GalN-induced liver injury in LECT2-deficient mice.

Keywords

GPT, glutamic pyruvic transaminase; Interferon-γ; LECT2, leukocyte cell-derived chemotaxin 2; LPS, lipopolysaccharide; LPS/d-GalN-induced liver injury; Leukocyte cell-derived chemotaxin 2; MNC, mononuclear cell; d-GalN, d-galactosamine.

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