title: Interferon-alpha/beta upregulate IL-15 expression in vitro and in vivo: analysis in human hepatocellular carcinoma cell lines and in chronic hepatitis C patients during interferon-alpha/beta treatment.
abstract: Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2, and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both IFN-alpha and -beta dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-beta showed stronger activity in IL-15 production induction in vitro than IFN-alpha. For in vivo examination, sera were obtained from 21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA. The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and significantly increased only during the IFN administration period. These results confirm that IFN-alpha/beta induce IL-15 production and also suggest that IL-15 may be associated with type I IFN-induced immune response.
authors.affiliation: Department of General Medicine, Kyushu University Hospital, 3-3-1, Maidashi Higashiku, Fukuoka, 812-8582, Japan. kyamaji@genmedpr.med.kyushu-u.ac.jp
authors.forename: Kouzaburo
authors.initials: K
authors.lastname: Yamaji
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nabeshima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.forename: Yong
authors.initials: Y
authors.lastname: Chong
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikematsu
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D016899:Interferon-beta / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D019409:Interleukin-15 / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D019409:Interleukin-15; D016899:Interferon-beta