AMBROŽOVÁ, Gabriela, Hana VEREŠČÁKOVÁ, Adolf KOUDELKA, Thorben RAVEKES, Tanja K. RUDOLPH, Anna KLINKE, Volker RUDOLPH, Bruce A. FREEMAN, Steven R. WOODCOCK, Lukáš KUBALA and Michaela PEKAROVÁ. Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses. FREE RADICAL BIOLOGY AND MEDICINE. New York, NY, USA: ELSEVIER SCIENCE INC, 2016, vol. 90, January, p. 252-260. ISSN 0891-5849. Available from: https://dx.doi.org/10.1016/j.freeradbiomed.2015.11.026.
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Basic information
Original name Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses
Authors AMBROŽOVÁ, Gabriela (203 Czech Republic), Hana VEREŠČÁKOVÁ (203 Czech Republic, belonging to the institution), Adolf KOUDELKA (203 Czech Republic, belonging to the institution), Thorben RAVEKES (276 Germany), Tanja K. RUDOLPH (276 Germany), Anna KLINKE (276 Germany), Volker RUDOLPH (276 Germany), Bruce A. FREEMAN (840 United States of America), Steven R. WOODCOCK (840 United States of America), Lukáš KUBALA (203 Czech Republic) and Michaela PEKAROVÁ (703 Slovakia).
Edition FREE RADICAL BIOLOGY AND MEDICINE, New York, NY, USA, ELSEVIER SCIENCE INC, 2016, 0891-5849.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 5.606
RIV identification code RIV/00216224:14310/16:00094207
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.026
UT WoS 000367396600023
Keywords in English Nitro-fatty acids; Nitro-oleic acid; Macrophages; Macrophage functional specialization; Fibrosis; Inflammation
Tags AKR, rivok
Changed by Changed by: Ing. Andrea Mikešková, učo 137293. Changed: 11/5/2017 18:18.
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.
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