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NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF- κ B Signaling Pathway

View Article: PubMed Central - PubMed

ABSTRACT

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-α and NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-α and IL-1β secretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

No MeSH data available.


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Effect of NBD on NOX1, NOX2, and NOX4 expression in the lung tissues of mice with ALI. (a) Relative NOX1, NOX2, NOX4, and β-actin immunointensity levels were calculated. (b) Statistical results. NOX1, NOX2, and NOX4 expression levels were increased by LPS administration, and these changes were inhibited by the middle and large NBD concentrations. Data are expressed as the mean ± SD (n = 6). A represents versus control group, AP < 0.05; B represents versus model group, BP < 0.05; C represents versus N-NBD group, CP < 0.05; D represents versus NBD-2 group, DP < 0.05; E represents versus NBD-6 group, EP < 0.05.
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fig8: Effect of NBD on NOX1, NOX2, and NOX4 expression in the lung tissues of mice with ALI. (a) Relative NOX1, NOX2, NOX4, and β-actin immunointensity levels were calculated. (b) Statistical results. NOX1, NOX2, and NOX4 expression levels were increased by LPS administration, and these changes were inhibited by the middle and large NBD concentrations. Data are expressed as the mean ± SD (n = 6). A represents versus control group, AP < 0.05; B represents versus model group, BP < 0.05; C represents versus N-NBD group, CP < 0.05; D represents versus NBD-2 group, DP < 0.05; E represents versus NBD-6 group, EP < 0.05.

Mentions: Inflammation-induced oxidative stress plays an important role in ALI. Our previous results indicated that the NF-κB signaling pathway regulates NOX family expression, thereby inducing increased reactive oxygen species production leading to cellular oxidative damage. Notably, LPS stimulation significantly increased NOX1, NOX2, and NOX4 expression, while pretreatment with the middle and large NBD concentrations suppressed LPS-induced NOX family member expression (Figures 8(a) and 8(b)). These results demonstrated that NBD attenuates LPS-induced oxidative stress in ALI by inhibiting NOX production. Similar results were observed via IHC staining and semiquantitative analysis (Figure 9).


NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF- κ B Signaling Pathway
Effect of NBD on NOX1, NOX2, and NOX4 expression in the lung tissues of mice with ALI. (a) Relative NOX1, NOX2, NOX4, and β-actin immunointensity levels were calculated. (b) Statistical results. NOX1, NOX2, and NOX4 expression levels were increased by LPS administration, and these changes were inhibited by the middle and large NBD concentrations. Data are expressed as the mean ± SD (n = 6). A represents versus control group, AP < 0.05; B represents versus model group, BP < 0.05; C represents versus N-NBD group, CP < 0.05; D represents versus NBD-2 group, DP < 0.05; E represents versus NBD-6 group, EP < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig8: Effect of NBD on NOX1, NOX2, and NOX4 expression in the lung tissues of mice with ALI. (a) Relative NOX1, NOX2, NOX4, and β-actin immunointensity levels were calculated. (b) Statistical results. NOX1, NOX2, and NOX4 expression levels were increased by LPS administration, and these changes were inhibited by the middle and large NBD concentrations. Data are expressed as the mean ± SD (n = 6). A represents versus control group, AP < 0.05; B represents versus model group, BP < 0.05; C represents versus N-NBD group, CP < 0.05; D represents versus NBD-2 group, DP < 0.05; E represents versus NBD-6 group, EP < 0.05.
Mentions: Inflammation-induced oxidative stress plays an important role in ALI. Our previous results indicated that the NF-κB signaling pathway regulates NOX family expression, thereby inducing increased reactive oxygen species production leading to cellular oxidative damage. Notably, LPS stimulation significantly increased NOX1, NOX2, and NOX4 expression, while pretreatment with the middle and large NBD concentrations suppressed LPS-induced NOX family member expression (Figures 8(a) and 8(b)). These results demonstrated that NBD attenuates LPS-induced oxidative stress in ALI by inhibiting NOX production. Similar results were observed via IHC staining and semiquantitative analysis (Figure 9).

View Article: PubMed Central - PubMed

ABSTRACT

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5&thinsp;mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced I&kappa;B-&alpha; and NF-&kappa;Bp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-&alpha; and IL-1&beta; secretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

No MeSH data available.


Related in: MedlinePlus