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Villacorta, Luis; Minarrieta, Lucia; Salvatore, Sonia R.; Khoo, Nicholas K.; Rom, Oren; Gao, Zhen; Berman, Rebecca C.; Jobbagy, Soma; Li, Lihua; Woodcock, Steven R.; Chen, Y. Eugene; Freeman, Bruce A.; Ferreira, Ana M.; Schopfer, Francisco J.; Vitturi, Dario A.
Redox biology, 05/2018, Volume: 15, Issue: CJournal Article
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. Display omitted
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