In Situ Generation, Metabolism and Immunomodulatory Signaling Actions of Nitro-conjugated Linoleic Acid in a Murine Model of Inflammation

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2018 Feb 8

PMID 29413964

Citations 41

Authors

Luis Villacorta

Lucia Minarrieta

Sonia R Salvatore

Nicholas K Khoo

Oren Rom

Zhen Gao

Rebecca C Berman

Soma Jobbagy

Lihua Li

Steven R Woodcock

Y Eugene Chen

Bruce A Freeman

Ana M Ferreira

Francisco J Schopfer

Dario A Vitturi

Affiliations

Soon will be listed here.

Abstract

Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitro-conjugated linoleic acid (NO-CLA). Herein, NO-CLA generation is demonstrated within the context of acute inflammatory responses both in vitro and in vivo. Macrophage activation resulted in dose- and time-dependent CLA nitration and also in the production of secondary electrophilic and non-electrophilic derivatives. Both exogenous NO-CLA as well as that generated in situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory cytokine production and up-regulated Nrf2-regulated proteins. Importantly, both CLA nitration and the corresponding downstream anti-inflammatory actions of NO-CLA were recapitulated in a mouse peritonitis model where NO-CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO-CLA has the potential to function as an adaptive response capable of not only modulating inflammation amplitude but also protecting neighboring tissues via the expression of Nrf2-dependent genes.

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