Nox2 and Nox4 mediate tumour necrosis factor-α-induced ventricular remodelling in mice.
Bottom Line: ROS was significantly decreased by inhibitors of NADPH oxidase, but not by inhibitors of other ROS production systems.Nox2 and Nox4 siRNA significantly attenuated TNF-α-induced ROS and upregulation of IL-1β and IL-6 in cardiomyocytes.Our study highlights a novel TNF-α-induced chronic ventricular remodelling mechanism mediated by sequential regulation of Nox2 and Nox4 subunits.
Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. email@example.comShow MeSH
Related in: MedlinePlus
Mentions: We measured IL-1β, IL-2, IL-6 and TNF-α protein concentrations in ventricular tissue lysates. All four cytokines in mice injected with TNF-α were significantly elevated compared to controls until 28 days post-injection (Fig. 3). IL-1β concentrations of TNF-α-injected mice were significantly elevated at 7 days post-injection compared to controls and more than 170% increased compared to TNF-α-injected mice 1 day post-injection (Fig. 3A). IL-1β remained elevated until 28 days post-injection and was significantly higher than controls. Progressive elevation of IL-2 and IL-6 concentrations were observed in mice injected with TNF-α 7 and 28 days previously, whereas TNF-α-injected mice 1 day post-injection showed the same level compared to controls (Fig. 3B and C). TNF-α protein concentrations in the ventricular tissue of TNF-α-injected mice were significantly increased at all three time points (Fig. 3D). These elevated levels of pro-inflammatory cytokines showed that ventricles of TNF-α injected mice are inflamed.
Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. firstname.lastname@example.org