Document Detail


Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases.
MedLine Citation:
PMID:  23045702     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elucidating the molecular pathways active in pathologic tissues has important implications for defining disease subsets, selecting therapy, and monitoring disease activity. The development of therapeutics directed at IFN-α or IFN-γ makes the discovery of probes that report precisely on the activity of different IFN pathways a high priority. We show that, although type I and II IFNs induce the expression of a largely overlapping group of molecules, precise probes of IFN-γ activity can be defined. Used in combination, these probes show prominent IFN-γ effects in Sjögren syndrome (SS) tissues. In contrast, dermatomyositis muscle shows a dominant type I IFN pattern. Interestingly, heterogeneity of IFN signatures exists in patients with SS, with some patients demonstrating a predominant type I pattern. The biochemical patterns largely distinguish the target tissues in patients with SS from those with dermatomyositis and provide a relative weighting of the effects of distinct IFN pathways in specific biopsies. In SS, type I and II IFN effects are localized to the same epithelial cells, surrounded by inflammatory cells expressing IFN-γ-induced proteins, suggesting reinforcing interactions. Precise probes of the different IFN pathways active in tissues of complex rheumatic diseases will be critical to classify disease, elucidate pathogenesis, and select therapy.
Authors:
John C Hall; Livia Casciola-Rosen; Alan E Berger; Efstathia K Kapsogeorgou; Chris Cheadle; Athanasios G Tzioufas; Alan N Baer; Antony Rosen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-08-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17609-14     Citation Subset:  IM    
Affiliation:
Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE41291
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MeSH Terms
Descriptor/Qualifier:
Epithelial Cells / metabolism
Gene Expression Regulation / physiology
Humans
Interferon-gamma / metabolism,  physiology*
Rheumatic Diseases / physiopathology*
Salivary Glands / cytology,  metabolism
Grant Support
ID/Acronym/Agency:
AR 053503/AR/NIAMS NIH HHS; AR 44684/AR/NIAMS NIH HHS; DE 12354/DE/NIDCR NIH HHS; DE 12354-12S1/DE/NIDCR NIH HHS; P30 AR053503/AR/NIAMS NIH HHS; R01 AR044684/AR/NIAMS NIH HHS; R37 DE012354/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
82115-62-6/Interferon-gamma
Comments/Corrections

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