| Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases. | |
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MedLine Citation:
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PMID: 23045702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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John C Hall; Livia Casciola-Rosen; Alan E Berger; Efstathia K Kapsogeorgou; Chris Cheadle; Athanasios G Tzioufas; Alan N Baer; Antony Rosen |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Validation Studies Date: 2012-10-08 |
Journal Detail:
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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:
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Created Date: 2012-10-24 Completed Date: 2013-01-07 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 17609-14 Citation Subset: IM |
Affiliation:
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Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE41291 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Epithelial Cells
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metabolism Gene Expression Regulation / physiology Humans Interferon-gamma / metabolism, physiology* Rheumatic Diseases / physiopathology* Salivary Glands / cytology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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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 |
| Chemical | |
Reg. No./Substance:
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82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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