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In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation.
Villacorta, Luis Minarrieta, Lucia Salvatore, Sonia R Khoo, Nicholas K Rom, Oren Gao, Zhen Berman, Rebecca C Jobbagy, Soma Li, Lihua Woodcock, Steven R
Villacorta, Luis
Minarrieta, Lucia
Salvatore, Sonia R
Khoo, Nicholas K
Rom, Oren
Gao, Zhen
Berman, Rebecca C
Jobbagy, Soma
Li, Lihua
Woodcock, Steven R
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2018-05
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Abstract
Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitro-conjugated linoleic acid (NO2-CLA). Herein, NO2-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 NO2-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 NO2-CLA were recapitulated in a mouse peritonitis model where NO2-CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO2-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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In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. 2018, 15:522-531 Redox Biol
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en
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2213-2317