The human interferon ? species and receptors

Pestka, Sidney

doi:10.1002/1097-0282(2000)55:4<254::aid-bip1001>3.0.co;2-1

Cited by 148 publications

(124 citation statements)

References 218 publications

(352 reference statements)

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“…Two types of IFNs, type I and II, are defined by their interaction with cognate receptors, type I or II receptors, respectively (Pestka, 1997;Stark et al, 1998 (Pestka, 2000). Although each receptor requires specific signal transduction components, both receptors interact with JAK family protein tyrosine kinases that phosphorylate (Stark et al, 1998;Samuel, 2001).…”

Section: Discussionmentioning

confidence: 99%

Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene

et al. 2003

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“…1 In addition to its critical roles in host defense, IFN-a has also been demonstrated to have several central nervous system (CNS) effects ranging from increased neuronal excitabilities 2 and regulation of temperature, 3 circadian rhythm 4 and sleep 3 to ingestive behavior 5 and emotion. 6 Despite wide therapeutic application of IFN-a in chronic viral infections and in several types of malignancies, there is mounting evidence that IFN-a is associated with brain damage in several clinical conditions including HIV-associated dementia, 7 CNS lupus 8 and familial Aicardi-Goutieres syndrome.…”

Section: Introductionmentioning

confidence: 99%

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

2007

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The prime anti-viral cytokine interferon-a (IFN-a) has been implicated in several central nervous system (CNS) disorders in addition to its beneficial effects. Systemic IFN-a treatment causes severe neuropsychiatric complications in humans, including depression, anxiety and cognitive impairments. While numerous neuromodulatory effects by IFN-a have been described, it remains unresolved whether or not systemic IFN-a acts directly on the brain to execute its CNS actions. In the present study, we have analyzed the genes directly regulated in post-IFN-a receptor signaling and found that intraperitoneal administration of mouse IFN-a, but not human IFN-a, activated expression of several prototypic IFN-stimulated genes (ISGs), in particular signal transducers and activators of transcription (STAT1), IFN-induced 15 kDa protein (ISG15), ubiquitin-specific proteinase 18 (USP18) and guanylate-binding protein 3 (GBP3) in the brain. A similar temporal profile for the regulated expression of these IFN-aactivated ISG genes was observed in the brain compared with the peripheral organs. Dual labeling in situ hybridization combined with immunocytochemical staining demonstrated a wide distribution of the key IFN-regulated gene STAT1 transcripts in the different parenchyma cells of the brain, particularly neurons. The overall response to IFN-a challenge was abolished in STAT1 knockout mice. Together, our results indicate a direct, STAT1-dependent action of systemic IFN-a in the CNS, which may provide the basis for a mechanism in humans for neurological/neuropsychiatric illnesses associated with IFN-a therapy.

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“…The main question at issue is whether their activity is redundant or they are characterized by unique functions (6). Studies of the biological effects of natural IFN subtypes have shown that their activities can vary greatly (7)(8)(9)(10). IFN-␣8, for example, is the most potent antiviral protein (11), while IFN-␤ has a higher potency in inhibiting the growth of certain tumors and is used in the treatment of multiple sclerosis (12)(13)(14).…”

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confidence: 99%

Regulatory Effect of IFN-κ, A Novel Type I IFN, On Cytokine Production by Cells of the Innate Immune System

Nardelli

Zaritskaya

Semenuk

et al. 2002

The Journal of Immunology

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IFN-κ 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-κ on cells of the innate immune system by comparing cytokine release following treatment of human cells with either IFN-κ or two recombinant IFN subtypes, IFN-β and IFN-α2a. Although IFN-α2a failed to stimulate monocyte cytokine secretion, IFN-κ, like IFN-β, induced the release of several cytokines from both monocytes and dendritic cells, without the requirement of a costimulatory signal. IFN-κ was particularly effective in inhibiting inducible IL-12 release from monocytes. Unlike IFN-β, IFN-κ did not induce release of IFN-γ by PBL. Expression of the IFN-κ mRNA was observed in resting dendritic cells and monocytes, and it was up-regulated by IFN-γ stimulation in monocytes, while IFN-β mRNA was minimally detectable under the same conditions. Monocyte and dendritic cell expression of IFN-κ was also confirmed in vivo in chronic lesions of psoriasis vulgaris and atopic dermatitis. Finally, biosensor-based binding kinetic analysis revealed that IFN-κ, like IFN-β, binds strongly to heparin (Kd: 2.1 nM), suggesting that the cytokine can be retained close to the local site of production. The pattern of cytokines induced by IFN-κ in monocytes, coupled with the unique induction of IFN-κ mRNA by IFN-γ, indicates a potential role for IFN-κ in the regulation of immune cell functions.

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The human interferon ? species and receptors

Cited by 148 publications

References 218 publications

Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene

Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

Regulatory Effect of IFN-κ, A Novel Type I IFN, On Cytokine Production by Cells of the Innate Immune System

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