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Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis.
Minayoshi, Yuki; Maeda, Hitoshi; Hamasaki, Keisuke; Nagasaki, Taisei; Takano, Mei; Fukuda, Ryo; Mizuta, Yuki; Tanaka, Motohiko; Sasaki, Yutaka; Otagiri, Masaki; Watanabe, Hiroshi; Maruyama, Toru.
Afiliación
  • Minayoshi Y; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Maeda H; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Hamasaki K; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Nagasaki T; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Takano M; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Fukuda R; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Mizuta Y; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Tanaka M; Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
  • Sasaki Y; Public Health and Welfare Bureau, 5-1-1 Oe, Chuo-ku, Kumamoto 862-0971, Japan.
  • Otagiri M; Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
  • Watanabe H; Osaka Central Hospital, 3-3-30 Umeda, Kita-ku, Osaka 530-0001, Japan.
  • Maruyama T; Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 19.
Article en En | MEDLINE | ID: mdl-38399475
ABSTRACT
Although a lot of effort has been put into creating drugs and combination therapies against chronic hepatitis, no effective treatment has been established. Type-I interferon is a promising therapeutic for chronic hepatitis due to its excellent anti-inflammatory effects through interferon receptors on hepatic macrophages. To develop a type-I IFN equipped with the ability to target hepatic macrophages through the macrophage mannose receptor, the present study designed a mouse type-I interferon-mannosylated albumin fusion protein using site-specific mutagenesis and albumin fusion technology. This fusion protein exhibited the induction of anti-inflammatory molecules, such as IL-10, IL-1Ra, and PD-1, in RAW264.7 cells, or hepatoprotective effects on carbon tetrachloride-induced chronic hepatitis mice. As expected, such biological and hepatoprotective actions were significantly superior to those of human fusion proteins. Furthermore, the repeated administration of mouse fusion protein to carbon tetrachloride-induced chronic hepatitis mice clearly suppressed the area of liver fibrosis and hepatic hydroxyproline contents, not only with a reduction in the levels of inflammatory cytokine (TNF-α) and fibrosis-related genes (TGF-ß, Fibronectin, Snail, and Collagen 1α2), but also with a shift in the hepatic macrophage phenotype from inflammatory to anti-inflammatory. Therefore, type-I interferon-mannosylated albumin fusion protein has the potential as a new therapeutic agent for chronic hepatitis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza