Regulatory effect of IFN-kappa, a novel type I IFN, on cytokine production by cells of the innate immune system.
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.
Nardelli
Bernardetta
B
Human Genome Sciences, Rockville, MD 20850, USA. bernardetta_nardelli@hgsi.com
Zaritskaya
Liubov
L
Semenuk
Mark
M
Cho
Yun Hee
YH
LaFleur
David W
DW
Shah
Devanshi
D
Ullrich
Stephen
S
Girolomoni
Giampiero
G
Albanesi
Cristina
C
Moore
Paul A
PA
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
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