| Local Tissue Expression of the Cell Death Ligand, FasL, Plays a Central Role in the Development of Extra-Pulmonary Acute Lung Injury. | |
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MedLine Citation:
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PMID: 21451443 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Indirect Acute Lung Injury (ALI) is a common manifestation in critically ill patients. Using a model of indirect ALI in mice, our lab has shown that local/pulmonary inhibition of extrinsic death receptor protein (Fas) leads to a decrease in lung inflammation and improved survival. However it is unknown if local, i.e., autocrine/paracrine inhibition of Fas ligand (FasL) affects on Fas expressing target cells itself or blockade of the actions of a more distal/endocrine source of FasL that accounts for these findings. METHODS: In order to examine this we used a model of indirect ALI in mice (dual insult of hemorrhagic shock followed 24hrs later by cecal ligation and puncture, in which animals received FasL siRNA intra-trachealy (IT; local silencing) or intravenously (IV; systemic/distal delivery) post-hemorrhage. RESULTS: After IT delivery of FasL siRNA there was a significant decrease in inflammatory cytokines, myeloperoxidase activity, and caspase-3 activity in lung tissue along with protein leak as compared to controls. There was no difference found in these various outcome markers between those treated with FasL siRNA IV versus controls. CONCLUSIONS: The observation that local silencing of FasL, as opposed to distal/systemic silencing, ameliorates the effects of indirect ALI suggest not only that FasL produced in an autocrine/paracrine fashion in local tissues has pathological consequences within the lungs, but that FasL might be a valuable pulmonary therapeutic target. |
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Authors:
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Rajan K Thakkar; Chun-Shiang Chung; Yaping Chen; Sean F Monaghan; Joanne Lomas-Neira; Daithi S Heffernan; William G Cioffi; Alfred Ayala |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-29 |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: - ISSN: 1540-0514 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Shock-Trauma Research Laboratories, Department of Surgery, Division of Surgical Research, Rhode Island Hospital/the Alpert School of Medicine at Brown University, 593 Eddy Street, Providence, RI 02903. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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