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ID 115087
Author
Minayoshi, Yuki Kumamoto University
Maeda, Hitoshi Kumamoto University
Yanagisawa, Hiroki Kumamoto University
Hamasaki, Keisuke Kumamoto University
Mizuta, Yuki Kumamoto University
Nishida, Kento Kumamoto University
Kinoshita, Ryo Kumamoto University
Enoki, Yuki Kumamoto University
Imafuku, Tadasi Kumamoto University
Chuang, Victor Tuan Giam Monash University Malaysia
Koga, Tomoaki Kumamoto University
Fujiwara, Yukio Kumamoto University
Takeya, Motohiro Kumamoto University
Sonoda, Kayoko Kumamoto University
Wakayama, Tomohiko Kumamoto University
Taguchi, Kazuaki Sojo University
Iwakiri, Yasuko Yale University
Tanaka, Motohiko Kumamoto University
Sasaki, Yutaka Kumamoto University
Watanabe, Hiroshi Kumamoto University
Otagiri, Masaki Sojo University
Maruyama, Toru Kumamoto University
Keywords
Type-I interferon
Kupffer cell
albumin fusion technology
mannose
anti-inflammation
immunomodulation
Content Type
Journal Article
Description
Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
Journal Title
Drug Delivery
ISSN
10717544
15210464
NCID
AA10999339
Publisher
Taylor & Francis
Volume
25
Issue
1
Start Page
1055
End Page
1065
Published Date
2018-04-24
Rights
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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DOI (Published Version)
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language
eng
TextVersion
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departments
Pharmaceutical Sciences