| TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. | |
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MedLine Citation:
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PMID: 21044893 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The pleiotropic growth factor TGFβ(1) promotes many of the pathogenic mechanisms observed in lung fibrosis and airway remodeling, such as aberrant extracellular matrix deposition due to both fibroblast activation and fibroblast to myofibroblast differentiation. Serum amyloid P (SAP), a member of the pentraxin family of proteins inhibits bleomycin-induced lung fibrosis through an inhibition of pulmonary fibrocyte and pro-fibrotic alternative (M2) macrophage accumulation. It is unknown if SAP has effects downstream of TGFβ(1), a major mediator of pulmonary fibrosis. Using the lung specific TGFβ(1) transgenic mouse model, we determined that SAP inhibits all of the pathologies driven by TGFβ(1) including apoptosis, airway inflammation, pulmonary fibrocyte accumulation and collagen deposition, without affecting levels of TGFβ(1). To explore the role of monocyte derived cells in this model we used liposomal clodronate to deplete pulmonary macrophages. This led to pronounced anti-fibrotic effects that were independent of fibrocyte accumulation. Administration of SAP mirrored these effects and reduced both pulmonary M2 macrophages and increased chemokine IP10/CXCL10 expression in a SMAD 3-independent manner. Interestingly, SAP concentrations were reduced in the circulation of IPF patients and correlated with disease severity. Last, SAP directly inhibited M2 macrophage differentiation of monocytes obtained from these patients. These data suggest that the beneficial anti-fibrotic effects of SAP in TGFβ(1)-induced lung disease are via modulating monocyte responses. |
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Authors:
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Lynne A Murray; Qingsheng Chen; Michael S Kramer; David P Hesson; Rochelle L Argentieri; Xueyang Peng; Mridu Gulati; Robert J Homer; Thomas Russell; Nico van Rooijen; Jack A Elias; Cory M Hogaboam; Erica L Herzog |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-29 |
Journal Detail:
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Title: The international journal of biochemistry & cell biology Volume: 43 ISSN: 1878-5875 ISO Abbreviation: Int. J. Biochem. Cell Biol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508482 Medline TA: Int J Biochem Cell Biol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 154-62 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Promedior, Inc. 371 Phoenixville Pike, Malvern, PA, USA. |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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K08 HL079066/HL/NHLBI NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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