Nitro-oleic acid modulates classical and regulatory activation
of macrophages and their involvement in pro-fibrotic responses

J 2016

Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses

AMBROŽOVÁ, Gabriela, Hana VEREŠČÁKOVÁ, Adolf KOUDELKA, Thorben RAVEKES, Tanja K. RUDOLPH et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{1355488,
   author = {Ambrožová, Gabriela and Vereščáková, Hana and Koudelka, Adolf and Ravekes, Thorben and Rudolph, Tanja K. and Klinke, Anna and Rudolph, Volker and Freeman, Bruce A. and Woodcock, Steven R. and Kubala, Lukáš and Pekarová, Michaela},
   article_location = {New York, NY, USA},
   article_number = {January},
   doi = {http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.026},
   keywords = {Nitro-fatty acids; Nitro-oleic acid; Macrophages; Macrophage functional specialization; Fibrosis; Inflammation},
   language = {eng},
   issn = {0891-5849},
   journal = {FREE RADICAL BIOLOGY AND MEDICINE},
   title = {Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses},
   url = {https://www.ncbi.nlm.nih.gov/pubmed/26620549},
   volume = {90},
   year = {2016}
}

TY  - JOUR
ID  - 1355488
AU  - Ambrožová, Gabriela - Vereščáková, Hana - Koudelka, Adolf - Ravekes, Thorben - Rudolph, Tanja K. - Klinke, Anna - Rudolph, Volker - Freeman, Bruce A. - Woodcock, Steven R. - Kubala, Lukáš - Pekarová, Michaela
PY  - 2016
TI  - Nitro-oleic acid modulates classical and regulatory activation of macrophages and their involvement in pro-fibrotic responses
JF  - FREE RADICAL BIOLOGY AND MEDICINE
VL  - 90
IS  - January
SP  - 252-260
EP  - 252-260
PB  - ELSEVIER SCIENCE INC
SN  - 08915849
KW  - Nitro-fatty acids
KW  - Nitro-oleic acid
KW  - Macrophages
KW  - Macrophage functional specialization
KW  - Fibrosis
KW  - Inflammation
UR  - https://www.ncbi.nlm.nih.gov/pubmed/26620549
N2  - 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.
ER  -

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. \textit{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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