학술논문
Regulation of Versican Expression in Macrophages is Mediated by Canonical Type I Interferon Signaling via ISGF3.
Document Type
Author
Chang MY; Department of Comparative Medicine, University of Washington, Seattle, WA.; Center for Lung Biology, University of Washington at South Lake Union, Seattle, WA.; Chan CK; Department of Comparative Medicine, University of Washington, Seattle, WA.; Center for Lung Biology, University of Washington at South Lake Union, Seattle, WA.; Brune JE; Department of Comparative Medicine, University of Washington, Seattle, WA.; Center for Lung Biology, University of Washington at South Lake Union, Seattle, WA.; Manicone AM; Center for Lung Biology, University of Washington at South Lake Union, Seattle, WA.; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Bomsztyk K; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA.; Frevert CW; Department of Comparative Medicine, University of Washington, Seattle, WA.; Center for Lung Biology, University of Washington at South Lake Union, Seattle, WA.; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Altemeier WA; Center for Lung Biology, University of Washington at South Lake Union, Seattle, WA.; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.
Source
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Growing evidence supports a role for versican as an important component of the inflammatory response, with both pro- and anti-inflammatory roles depending on the specific context of the system or disease under investigation. Our goal is to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. In previous work, we showed that LPS triggers a signaling cascade involving TLR4, the Trif adaptor, type I interferons, and the type I interferon receptor, leading to increased versican expression by macrophages. In the present study, we used a combination of chromatin immunoprecipitation, siRNA, chemical inhibitors, and mouse model approaches to investigate the regulatory events downstream of the type I interferon receptor to better define the mechanism controlling versican expression. Results indicate that transcriptional regulation by canonical type I interferon signaling via the heterotrimeric transcription factor, ISGF3, controls versican expression in macrophages exposed to LPS. This pathway is not dependent on MAPK signaling, which has been shown to regulate versican expression in other cell types. The stability of versican mRNA may also contribute to prolonged versican expression in macrophages. These findings strongly support a role for macrophage-derived versican as a type I interferon-stimulated gene and further our understanding of versican's role in regulating inflammation.
Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare.
Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare.