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Nox2 and Nox4 mediate tumour necrosis factor-α-induced ventricular remodelling in mice.

Moe KT, Yin NO, Naylynn TM, Khairunnisa K, Wutyi MA, Gu Y, Atan MS, Wong MC, Koh TH, Wong P - J. Cell. Mol. Med. (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. moe.kyaw.thu@nhc.com.sg

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Related in: MedlinePlus

Elevated pro-inflammatory cytokine concentrations in the ventricles of TNF-α-injected mice. The ventricular homogenates were used to determine the pro-inflammatory cytokine concentrations using Bioplex Multiplex Suspension Array System kits. The concentrations of IL-1β (A), IL-2 (B), IL-6 (C) and TNF-α (D) were shown. Data are expressed as pg/mg of ventricular protein ± S.D. *P < 0.05.
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fig03: Elevated pro-inflammatory cytokine concentrations in the ventricles of TNF-α-injected mice. The ventricular homogenates were used to determine the pro-inflammatory cytokine concentrations using Bioplex Multiplex Suspension Array System kits. The concentrations of IL-1β (A), IL-2 (B), IL-6 (C) and TNF-α (D) were shown. Data are expressed as pg/mg of ventricular protein ± S.D. *P < 0.05.

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.


Nox2 and Nox4 mediate tumour necrosis factor-α-induced ventricular remodelling in mice.

Moe KT, Yin NO, Naylynn TM, Khairunnisa K, Wutyi MA, Gu Y, Atan MS, Wong MC, Koh TH, Wong P - J. Cell. Mol. Med. (2011)

Elevated pro-inflammatory cytokine concentrations in the ventricles of TNF-α-injected mice. The ventricular homogenates were used to determine the pro-inflammatory cytokine concentrations using Bioplex Multiplex Suspension Array System kits. The concentrations of IL-1β (A), IL-2 (B), IL-6 (C) and TNF-α (D) were shown. Data are expressed as pg/mg of ventricular protein ± S.D. *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373429&req=5

fig03: Elevated pro-inflammatory cytokine concentrations in the ventricles of TNF-α-injected mice. The ventricular homogenates were used to determine the pro-inflammatory cytokine concentrations using Bioplex Multiplex Suspension Array System kits. The concentrations of IL-1β (A), IL-2 (B), IL-6 (C) and TNF-α (D) were shown. Data are expressed as pg/mg of ventricular protein ± S.D. *P < 0.05.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Research and Development Unit, National Heart Centre Singapore, Singapore. moe.kyaw.thu@nhc.com.sg

Show MeSH
Related in: MedlinePlus