Myeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization

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dc.contributor.authorLu, Gemingen
dc.contributor.authorZhang, Ruihuaen
dc.contributor.authorGeng, Shuoen
dc.contributor.authorPeng, Liangen
dc.contributor.authorJayaraman, Padminien
dc.contributor.authorChen, Chunen
dc.contributor.authorXu, Feifongen
dc.contributor.authorYang, Jianjunen
dc.contributor.authorLi, Qinen
dc.contributor.authorZheng, Haoen
dc.contributor.authorShen, Kimberlyen
dc.contributor.authorWang, Juanen
dc.contributor.authorLiu, Xiyuen
dc.contributor.authorWang, Weidongen
dc.contributor.authorZheng, Zihanen
dc.contributor.authorQi, Chen-Fengen
dc.contributor.authorSi, Chuanpingen
dc.contributor.authorHe, John Cijiangen
dc.contributor.authorLiu, Kebinen
dc.contributor.authorLira, Sergio A.en
dc.contributor.authorSikora, Andrew G.en
dc.contributor.authorLi, Liwuen
dc.contributor.authorXiong, Huabaoen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2017-11-13T19:43:18Zen
dc.date.available2017-11-13T19:43:18Zen
dc.date.issued2015-03-27en
dc.description.abstractHere we show that iNOS-deficient mice display enhanced classically activated M1 macrophage polarization without major effects on alternatively activated M2 macrophages. eNOS and nNOS mutant mice show comparable M1 macrophage polarization compared with wild-type control mice. Addition of N6-(1-iminoethyl)-L-lysine dihydrochloride, an iNOS inhibitor, significantly enhances M1 macrophage polarization while S-nitroso-N-acetylpenicillamine, a NO donor, suppresses M1 macrophage polarization. NO derived from iNOS mediates nitration of tyrosine residues in IRF5 protein, leading to the suppression of IRF5-targeted M1 macrophage signature gene activation. Computational analyses corroborate a circuit that fine-tunes the expression of IL-12 by iNOS in macrophages, potentially enabling versatile responses based on changing microenvironments. Finally, studies of an experimental model of endotoxin shock show that iNOS deficiency results in more severe inflammation with an enhanced M1 macrophage activation phenotype. These results suggest that NO derived from iNOS in activated macrophages suppresses M1 macrophage polarization.en
dc.identifier.doihttps://doi.org/10.1038/ncomms7676en
dc.identifier.urihttp://hdl.handle.net/10919/80357en
dc.identifier.volume6en
dc.language.isoen_USen
dc.publisherNatureen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titleMyeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarizationen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden

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