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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.


Related in: MedlinePlus

Effect of NBD on pNF-κBp65 expression, as determined via immunohistochemistry, in the lung tissues of mice with ALI. (a) Representative photographs of pNF-κB P65 expression in the lung (original magnification ×200). (A) Control group; (B) model group; (C) N-NBD group; (D) NBD-2 group; (E) NBD-6 group; (F) NBD-10 group. Black arrows indicate the immunohistochemically positive pNF-κBp65. (b) IHC staining scores pertaining to pNF-κB P65 expression. pNF-κBp65 expression levels were increased by LPS administration, and these changes were inhibited by NBD pretreatment in a concentration-dependent manner. 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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fig7: Effect of NBD on pNF-κBp65 expression, as determined via immunohistochemistry, in the lung tissues of mice with ALI. (a) Representative photographs of pNF-κB P65 expression in the lung (original magnification ×200). (A) Control group; (B) model group; (C) N-NBD group; (D) NBD-2 group; (E) NBD-6 group; (F) NBD-10 group. Black arrows indicate the immunohistochemically positive pNF-κBp65. (b) IHC staining scores pertaining to pNF-κB P65 expression. pNF-κBp65 expression levels were increased by LPS administration, and these changes were inhibited by NBD pretreatment in a concentration-dependent manner. 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: It is accepted that LPS induces NF-κB activation by acting on IKK and IκΒ phosphorylation in lung tissue and that this effect is related to the inflammatory response [21]. At 2 hours after LPS administration, IKK, IκΒ-α, and NF-κBp65 phosphorylation levels increased dramatically. However, these increases were significantly attenuated in a concentration-dependent manner in mice treated with NBD before LPS administration (Figures 6(a) and 6(b)). IHC staining and semiquantitative analysis yielded similar results (Figure 7).


NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF- κ B Signaling Pathway
Effect of NBD on pNF-κBp65 expression, as determined via immunohistochemistry, in the lung tissues of mice with ALI. (a) Representative photographs of pNF-κB P65 expression in the lung (original magnification ×200). (A) Control group; (B) model group; (C) N-NBD group; (D) NBD-2 group; (E) NBD-6 group; (F) NBD-10 group. Black arrows indicate the immunohistochemically positive pNF-κBp65. (b) IHC staining scores pertaining to pNF-κB P65 expression. pNF-κBp65 expression levels were increased by LPS administration, and these changes were inhibited by NBD pretreatment in a concentration-dependent manner. 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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fig7: Effect of NBD on pNF-κBp65 expression, as determined via immunohistochemistry, in the lung tissues of mice with ALI. (a) Representative photographs of pNF-κB P65 expression in the lung (original magnification ×200). (A) Control group; (B) model group; (C) N-NBD group; (D) NBD-2 group; (E) NBD-6 group; (F) NBD-10 group. Black arrows indicate the immunohistochemically positive pNF-κBp65. (b) IHC staining scores pertaining to pNF-κB P65 expression. pNF-κBp65 expression levels were increased by LPS administration, and these changes were inhibited by NBD pretreatment in a concentration-dependent manner. 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: It is accepted that LPS induces NF-κB activation by acting on IKK and IκΒ phosphorylation in lung tissue and that this effect is related to the inflammatory response [21]. At 2 hours after LPS administration, IKK, IκΒ-α, and NF-κBp65 phosphorylation levels increased dramatically. However, these increases were significantly attenuated in a concentration-dependent manner in mice treated with NBD before LPS administration (Figures 6(a) and 6(b)). IHC staining and semiquantitative analysis yielded similar results (Figure 7).

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