Publication details
Nitro-oleic acid attenuates the innate immune responses of macrophages stimulated with bacterial endotoxin.
| Authors | |
|---|---|
| Year of publication | 2012 |
| Type | Appeared in Conference without Proceedings |
| MU Faculty or unit | |
| Citation | |
| Description | Nitro-oleic acid attenuates the innate immune responses of macrophages stimulated with bacterial endotoxin G. Ambrozova1, 2, L. Kubala1, T. Rudolph3, A. Lojek1, T. Ravekes3, M. Pekarova1 1Institute of Biophysics AS CR, Brno, Czech Republic 2Masaryk University, Brno, Czech Republic 3Hamburg University Heart Center, Hamburg, Germany Background: Nitrated fatty acids (NO2-FAs) are generated as an adaptive response of organism to oxidative conditions. NO2-FAs were shown to exert significant anti-inflammatory signaling action in immune and vascular models; nevertheless, detailed mechanisms of their action in regulation of innate immune responses are not completely understood. Therefore, we investigated the role of nitro-oleic acid (OANO2) in endotoxin-stimulated RAW 264.7 macrophages. Materials and method: ATP test, luminol-enhanced chemiluminescence, Griess reaction, Western blot, amperometric, and TRAP assays were used for determination of OANO2-induced cytotoxicity, production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory mediators in macrophages, as well as expression of MAPKs, NF-kappaB, inducible nitric oxide synthase (iNOS), NADPH oxidase, CD36, and TLR2/4 receptors. Results: Our results showed that OANO2 significantly down regulated the activation of macrophages in a dose-dependent manner. Importantly, changes in the production of inflammatory mediators were associated with reduction of endotoxin-induced MAPK activation and expression of NF-kappaB. Beside that, we found OANO2-dependent inhibition of NADPH oxidase, iNOS, CD36, and TLR2/4 expression in endotoxin-stimulated RAW 264.7 cells. Conclusion: We can conclude that OANO2 is able to significantly reduce the oxidative and nitrative stress, generated within the macrophage-dependent innate immune responses, via the regulation of crucial intracellular signalling pathways connected with MAPK and NF-kappaB activation. |