title: Regulatory effect of IFN-kappa, a novel type I IFN, on cytokine production by cells of the innate immune system.
abstract: IFN-kappa is a recently identified type I IFN that exhibits both structural and functional homology with the other type I IFN subclasses. In this study, we have investigated the effect of IFN-kappa on cells of the innate immune system by comparing cytokine release following treatment of human cells with either IFN-kappa or two recombinant IFN subtypes, IFN-beta and IFN-alpha2a. Although IFN-alpha2a failed to stimulate monocyte cytokine secretion, IFN-kappa, like IFN-beta, induced the release of several cytokines from both monocytes and dendritic cells, without the requirement of a costimulatory signal. IFN-kappa was particularly effective in inhibiting inducible IL-12 release from monocytes. Unlike IFN-beta, IFN-kappa did not induce release of IFN-gamma by PBL. Expression of the IFN-kappa mRNA was observed in resting dendritic cells and monocytes, and it was up-regulated by IFN-gamma stimulation in monocytes, while IFN-beta mRNA was minimally detectable under the same conditions. Monocyte and dendritic cell expression of IFN-kappa was also confirmed in vivo in chronic lesions of psoriasis vulgaris and atopic dermatitis. Finally, biosensor-based binding kinetic analysis revealed that IFN-kappa, like IFN-beta, binds strongly to heparin (K(d): 2.1 nM), suggesting that the cytokine can be retained close to the local site of production. The pattern of cytokines induced by IFN-kappa in monocytes, coupled with the unique induction of IFN-kappa mRNA by IFN-gamma, indicates a potential role for IFN-kappa in the regulation of immune cell functions.
authors.affiliation: Human Genome Sciences, Rockville, MD 20850, USA. bernardetta_nardelli@hgsi.com
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Nardelli
authors.forename: Liubov
authors.initials: L
authors.lastname: Zaritskaya
authors.forename: Mark
authors.initials: M
authors.lastname: Semenuk
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: David W
authors.initials: DW
authors.lastname: LaFleur
authors.forename: Devanshi
authors.initials: D
authors.lastname: Shah
authors.forename: Stephen
authors.initials: S
authors.lastname: Ullrich
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Cristina
authors.initials: C
authors.lastname: Albanesi
authors.forename: Paul A
authors.initials: PA
authors.lastname: Moore
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: C062991:AZU1 protein, human; D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D016207:Cytokines; D007370:Interferon Type I; C439669:interferon kappa; D018664:Interleukin-12; D007371:Interferon-gamma; D006493:Heparin