| Interferon Regulatory Factor-1 Regulates the Autophagic Response in LPS Stimulated Macrophages through Nitric Oxide. | |
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MedLine Citation:
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PMID: 22105605 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The pathogenesis of sepsis is complex and unfortunately poorly understood. The cellular process of autophagy is believed to play a protective role in sepsis; however, the mechanisms responsible for its regulation in this setting are ill defined. In the present study, interferon regulatory factor-1 (IRF-1) was found to regulate the autophagic response in LPS stimulated macrophages. In vivo, tissue macrophages obtained from LPS stimulated IRF-1 knockout (KO) mice demonstrated increased autophagy and decreased apoptosis compared to those isolated from IRF-1 wild type (WT) mice. In vitro, LPS stimulated peritoneal macrophages obtained from IRF-1 KO mice experienced increased autophagy and decreased apoptosis. IRF-1 mediates the inhibition of autophagy by modulating the activation of the mammalian target of rapamycin (mTOR). LPS induced the activation of mTOR in WT peritoneal macrophages, but not in IRF-1 KO macrophages. In contrast, over-expression of IRF-1 alone increased the activation of mTOR and consequently decreased autophagic flux. Furthermore, the inhibitory effects of IRF-1 mTOR activity were mediated by nitric oxide (NO). Therefore, we propose a novel role for IRF-1 and NO in the regulation of macrophage autophagy during LPS stimulation, in which IRF-1/NO inhibits autophagy through mTOR activation. |
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Authors:
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Lemeng Zhang; Jon S Cardinal; Runalia Bahar; John Evankovich; Hai Huang; Gary Nace; Timothy R Billiar; Matthew R Rosengart; Pinhua Pan; Allan Tsung |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-09 |
Journal Detail:
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Title: Molecular medicine (Cambridge, Mass.) Volume: - ISSN: 1528-3658 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9501023 Medline TA: Mol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213 Department of Pulmonology, Xiangya Hospital, Central South University, Changsha, China, 410008. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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