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dc.contributor.authorMinayoshi, Y.
dc.contributor.authorMaeda, H.
dc.contributor.authorYanagisawa, H.
dc.contributor.authorHamasaki, K.
dc.contributor.authorMizuta, Y.
dc.contributor.authorNishida, K.
dc.contributor.authorKinoshita, R.
dc.contributor.authorEnoki, Y.
dc.contributor.authorImafuku, T.
dc.contributor.authorChuang, Victor
dc.contributor.authorKoga, T.
dc.contributor.authorFujiwara, Y.
dc.contributor.authorTakeya, M.
dc.contributor.authorSonoda, K.
dc.contributor.authorWakayama, T.
dc.contributor.authorTaguchi, K.
dc.contributor.authorIshima, Y.
dc.contributor.authorIshida, T.
dc.contributor.authorIwakiri, Y.
dc.contributor.authorTanaka, M.
dc.contributor.authorSasaki, Y.
dc.contributor.authorWatanabe, H.
dc.contributor.authorOtagiri, M.
dc.contributor.authorMaruyama, T.
dc.identifier.citationMinayoshi, Y. and Maeda, H. and Yanagisawa, H. and Hamasaki, K. and Mizuta, Y. and Nishida, K. and Kinoshita, R. et al. 2018. Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions. Drug Delivery. 25 (1): pp. 1067-1077.

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-IFNa2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNa2b, 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 IFNa2b, Man-HSA(D494N)-IFNa2b 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)-IFNa2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNa2b 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)-IFNa2b 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.

dc.publisherTaylor & Francis Inc.
dc.titleDevelopment of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions
dc.typeJournal Article
dcterms.source.titleDrug Delivery
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusFulltext not available

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