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. firstname.lastname@example.orgShow MeSH
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Mentions: Nox2 siRNA and Nox4 siRNA significantly decreased Nox2 and Nox4 mRNA levels by 45% and 80%, respectively, in adult human cardiomyocytes (Fig. 6A and B). However, Nox2 and Nox4 siRNA showed no changes in Nox4 and Nox2 mRNA, respectively (data not shown). The role of Nox2 and Nox4 in TNF-α-induced pro-inflammatory cytokine IL-1β and IL-6 expression, and ROS production was determined after knocking down Nox2 and Nox4. Nox2 siRNA significantly decreased TNF-α-induced upregulation of IL-1β by 50% and IL-6 by 25% (Fig. 6C and D). Nox4 siRNA also significantly decreased TNF-α-induced upregulation of IL-1β by 45% and IL-6 by 30%. Nox2 and Nox4 siRNA had no effect on IL-1β and IL-6 expression without TNF-α treatment. Control siRNA had no effect on TNF-α-induced upregulation of IL-1β and IL-6 (data not shown). Finally, Nox2 and Nox4 siRNA significantly decreased TNF-α-induced ROS production by 40% and 50%, respectively (Fig. 6E).
Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. email@example.com