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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 SOD and T-AOC activity and MDA concentrations in the lung tissues of mice with ALI. LPS challenge significantly increased MDA levels and decreased SOD and T-AOC activity compared with sham controls; however, treatment with the middle and large NBD concentrations exerted effects contrasting with those described above. 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.
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fig5: Effect of NBD on SOD and T-AOC activity and MDA concentrations in the lung tissues of mice with ALI. LPS challenge significantly increased MDA levels and decreased SOD and T-AOC activity compared with sham controls; however, treatment with the middle and large NBD concentrations exerted effects contrasting with those described above. 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.

Mentions: In general, the process of LPS-induced ALI is characterized by excessive oxidative stress, which damages endothelial barrier integrity [21]. SOD and T-AOC are antioxidant enzymes that are inactivated by reactions involving ROS and membrane phospholipids that form MDA. To assess the effects of NBD on MDA production in LPS-induced ALI, we detected SOD and T-AOC activity in the lung. LPS administration significantly decreased SOD levels (Figure 5(a)) and T-AOC (Figure 5(b)) activity and increased MDA (Figure 5(c)) levels. However, the middle and large NBD concentrations exerted effects contrasting with those of sham treatment. Therefore, we concluded that NBD attenuates ALI-induced oxidative stress in LPS-treated mice.


NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF- κ B Signaling Pathway
Effect of NBD on SOD and T-AOC activity and MDA concentrations in the lung tissues of mice with ALI. LPS challenge significantly increased MDA levels and decreased SOD and T-AOC activity compared with sham controls; however, treatment with the middle and large NBD concentrations exerted effects contrasting with those described above. 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5120201&req=5

fig5: Effect of NBD on SOD and T-AOC activity and MDA concentrations in the lung tissues of mice with ALI. LPS challenge significantly increased MDA levels and decreased SOD and T-AOC activity compared with sham controls; however, treatment with the middle and large NBD concentrations exerted effects contrasting with those described above. 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.
Mentions: In general, the process of LPS-induced ALI is characterized by excessive oxidative stress, which damages endothelial barrier integrity [21]. SOD and T-AOC are antioxidant enzymes that are inactivated by reactions involving ROS and membrane phospholipids that form MDA. To assess the effects of NBD on MDA production in LPS-induced ALI, we detected SOD and T-AOC activity in the lung. LPS administration significantly decreased SOD levels (Figure 5(a)) and T-AOC (Figure 5(b)) activity and increased MDA (Figure 5(c)) levels. However, the middle and large NBD concentrations exerted effects contrasting with those of sham treatment. Therefore, we concluded that NBD attenuates ALI-induced oxidative stress in LPS-treated mice.

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