Universität zu Köln

Ambrozova, Gabriela ORCID: 0000-0002-8172-9746, Martiskova, Hana, Koudelka, Adolf ORCID: 0000-0002-9998-8383, Ravekes, Thorben, Rudolph, Tanja K., Klinke, Anna, Rudolph, Volker, Freeman, Bruce A., Woodcock, Steven R., Kubala, Lukas ORCID: 0000-0002-7729-7338 and Pekarova, Michaela (2016). Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses. Free Radic. Biol. Med., 90. S. 252 - 261. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1873-4596

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Abstract

Inflammation is an immune response triggered by microbial invasion and/or tissue injury. While acute inflammation is directed toward invading pathogens and injured cells, thus enabling tissue regeneration, chronic inflammation can lead to severe pathologies and tissue dysfunction. These processes are linked with macrophage polarization into specific inflammatory M1-like or regulatory M2-like subsets. Nitro-fatty acids (NO2-FAs), produced endogenously as byproducts of metabolism and oxidative inflammatory conditions, may be useful for treating diseases associated with dysregulated immune homeostasis. The goal of this study was to characterize the role of nitro-oleic acid (OA-NO2) in regulating the functional specialization of macrophages induced by bacterial lipopolysaccharide or interleukin-4, and to reveal specific signaling mechanisms which can account for OA-NO2-dependent modulation of inflammation and fibrotic responses. Our results show that OA-NO2 inhibits lipopolysaccharide-stimulated production of both pro-inflammatory and immunoregulatory cytokines (including transforming growth factor-beta) and inhibits nitric oxide and superoxide anion production. OA-NO2 also decreases interleukin-4-induced macrophage responses by inhibiting arginase-I expression and transforming growth factor-beta production. These effects are mediated via downregulation of signal transducers and activators of transcription, mitogen-activated protein kinase and nuclear factor-kappa B signaling responses. Finally, OA-NO2 inhibits fibrotic processes in an in vivo model of angiotensin II-induced myocardial fibrosis by attenuating expression of alpha-smooth muscle actin, systemic transforming growth factor-beta levels and infiltration of both M1- and M2-like macrophage subsets into afflicted tissue. Overall, the electrophilic fatty acid derivative OA-NO2 modulates a broad range of M1- and M2-like macrophage functions and represents a potential therapeutic approach to target diseases associated with dysregulated macrophage subsets. (C) 2015 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ambrozova, Gabriela UNSPECIFIED orcid.org/0000-0002-8172-9746 UNSPECIFIED Martiskova, Hana UNSPECIFIED UNSPECIFIED UNSPECIFIED Koudelka, Adolf UNSPECIFIED orcid.org/0000-0002-9998-8383 UNSPECIFIED Ravekes, Thorben UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudolph, Tanja K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klinke, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudolph, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Freeman, Bruce A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Woodcock, Steven R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubala, Lukas UNSPECIFIED orcid.org/0000-0002-7729-7338 UNSPECIFIED Pekarova, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-291971
DOI:	10.1016/j.freeradbiomed.2015.11.026
Journal or Publication Title:	Free Radic. Biol. Med.
Volume:	90
Page Range:	S. 252 - 261
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1873-4596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NITRATED FATTY-ACIDS; INDUCED INFLAMMATION; 10-NITRO-OLEIC ACID; GENE-EXPRESSION; MURINE MODEL; PPAR-GAMMA; POLARIZATION; OXIDE; GENERATION; PLASTICITY Multiple languages Biochemistry & Molecular Biology; Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29197