| Adenosine promotes alternative macrophage activation via A2A and A2B receptors. | |
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MedLine Citation:
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PMID: 21926236 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adenosine has been implicated in suppressing the proinflammatory responses of classically activated macrophages induced by Th1 cytokines. Alternative macrophage activation is induced by the Th2 cytokines interleukin (IL)-4 and IL-13; however, the role of adenosine in governing alternative macrophage activation is unknown. We show here that adenosine treatment of IL-4- or IL-13-activated macrophages augments the expression of alternative macrophage markers arginase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and macrophage galactose-type C-type lectin-1. The stimulatory effect of adenosine required primarily A(2B) receptors because the nonselective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased both arginase activity (EC(50)=261.8 nM) and TIMP-1 production (EC(50)=80.67 nM), and both pharmacologic and genetic blockade of A(2B) receptors prevented the effect of NECA. A(2A) receptors also contributed to the adenosine augmentation of IL-4-induced TIMP-1 release, as both adenosine and NECA were less efficacious in augmenting TIMP-1 release by A(2A) receptor-deficient than control macrophages. Of the transcription factors known to drive alternative macrophage activation, CCAAT-enhancer-binding protein β was required, while cAMP response element-binding protein and signal transducer and activator of transcription 6 were dispensable in mediating the effect of adenosine. We propose that adenosine receptor activation suppresses inflammation and promotes tissue restitution, in part, by promoting alternative macrophage activation. |
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Authors:
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Balázs Csóka; Zsolt Selmeczy; Balázs Koscsó; Zoltán H Németh; Pál Pacher; Peter J Murray; Diane Kepka-Lenhart; Sidney M Morris; William C Gause; S Joseph Leibovich; György Haskó |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2011-09-16 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 26 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-01-04 Completed Date: 2012-02-27 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 376-86 Citation Subset: IM |
Affiliation:
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Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
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metabolism*,
pharmacology Adenosine-5'-(N-ethylcarboxamide) / pharmacology Animals Arginase / metabolism CCAAT-Enhancer-Binding Protein-beta / metabolism Cell Line Cyclic AMP Response Element-Binding Protein / metabolism Extracellular Space / metabolism Inflammation / immunology, metabolism* Interleukin-13 / metabolism Interleukin-4 / metabolism Macrophages / drug effects, immunology*, metabolism* Male Mice Mice, Inbred C57BL Mice, Knockout Receptor, Adenosine A2A / genetics, immunology, metabolism* Receptor, Adenosine A2B / genetics, immunology, metabolism* STAT6 Transcription Factor / metabolism Tissue Inhibitor of Metalloproteinase-1 / metabolism Toll-Like Receptor 4 / immunology, metabolism Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM066189/GM/NIGMS NIH HHS; R01GM57384/GM/NIGMS NIH HHS; R01GM66189/GM/NIGMS NIH HHS; R56 GM066189/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CCAAT-Enhancer-Binding Protein-beta; 0/Creb1 protein, mouse; 0/Cyclic AMP Response Element-Binding Protein; 0/Interleukin-13; 0/Receptor, Adenosine A2A; 0/Receptor, Adenosine A2B; 0/STAT6 Transcription Factor; 0/Stat6 protein, mouse; 0/Timp1 protein, mouse; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/Vasodilator Agents; 207137-56-2/Interleukin-4; 35920-39-9/Adenosine-5'-(N-ethylcarboxamide); 58-61-7/Adenosine; EC 3.5.3.1/Arg1 protein, mouse; EC 3.5.3.1/Arginase |
| Comments/Corrections | |
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