| Apoptotic neutrophils and nitric oxide regulate cytokine production by IFN-γ-stimulated macrophages. | |
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MedLine Citation:
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PMID: 21075005 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Early apoptotic neutrophils but not secondary necrotic ones down-regulate LPS-induced proinflammatory cytokine production of macrophages, thereby contributing to the resolution of inflammation. IFN-γ is also a well-known stimulant of macrophages, but how the apoptotic neutrophils affect IFN-γ-stimulated macrophages remains largely unexplored. Since IFN-γ induces the expression of inducible nitric oxide (NO) synthase, we examined the production of NO and various cytokines, including MIP-2, TNF-α, IL-12p40, IL-6, IL-10, and TGF-β, by IFN-γ-stimulated murine macrophages, the effect of coculturing the macrophages with early apoptotic or secondary necrotic neutrophils, and the regulatory role of NO in such cocultures. IFN-γ induced significant production of NO, IL-12p40, and IL-6 by macrophages, but not other cytokines. Early apoptotic neutrophils but not secondary necrotic ones promoted NO production, whereas secondary necrotic ones and their supernatants promoted TNF-α production. In contrast, both early apoptotic and secondary necrotic neutrophils suppressed IL-12p40 and IL-6 production. Furthermore, macrophages from inducible NO synthase-deficient mice produced significantly higher levels of MIP-2 than those from wild-type mice. Consistent with this, treatment of macrophages with l-NAME, an NO synthase inhibitor, also induced the production of a large amount of MIP-2. In conclusion, this study suggests that early apoptotic neutrophils are critical in the resolution of inflammation, but that secondary necrotic neutrophils may not cause an inflammatory response. Apoptotic neutrophils, however, appear not to modulate cytokine production via NO. |
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Authors:
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Takehiko Shibata; Kisaburo Nagata; Yoshiro Kobayashi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-12 |
Journal Detail:
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Title: Cytokine Volume: 53 ISSN: 1096-0023 ISO Abbreviation: Cytokine Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9005353 Medline TA: Cytokine Country: United States |
Other Details:
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Languages: eng Pagination: 191-5 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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