Immunopharmacological Potential of Selective Phosphodiesterase Inhibition. II. Evidence for the Involvement of an Inhibitory-κB/Nuclear Factor-κB-Sensitive Pathway in Alveolar Epithelial Cells

Staphylococcus aureus α-toxin is a pore-forming bacterial exotoxin that has been implicated as a significant virulence factor in human staphylococcal diseases. In primary cultures of rat pneumocyte type II cells and the human A549 alveolar epithelial cell line, purified α-toxin provoked rapid-onset phosphatidylinositol (PtdIns) hydrolysis as well as liberation of nitric oxide and the prostanoids PGE2, PGI2, and thromboxane A2. In addition, sustained upregulation of proinflammatory interleukin (IL)-8 mRNA expression and protein secretion occurred. “Priming” with low-dose IL-1β markedly enhanced the IL-8 response to α-toxin, which was then accompanied by IL-6 appearance. The cytokine response was blocked by the intracellular Ca2+-chelating reagent 1,2-bis(2-aminophenoxy)-ethane- N,N,N′ ,N′-tetraacetic acid, the protein kinase C inhibitor bis-indolyl maleimide I, as well as two independent inhibitors of nuclear factor-κB activation, pyrrolidine dithiocarbamate and caffeic acid phenethyl ester. We conclude that alveolar epithelial cells are highly reactive target cells of staphylococcal α-toxin. α-Toxin pore-associated transmembrane Ca2+flux and PtdIns hydrolysis-related signaling with downstream activation of protein kinase C and nuclear translocation of nuclear factor-κB are suggested to represent important underlying mechanisms. Such reactivity of the alveolar epithelial cells may be relevant for pathogenic sequelae in staphylococcal lung disease.

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Regulation of nuclear factor-κB, activator protein-1, and glutathione levels by tumor necrosis factor-α and dexamethasone in alveolar epithelial cells

Biochemical Pharmacology ◽

10.1016/s0006-2952(00)00392-0 ◽

2000 ◽

Vol 60 (8) ◽

pp. 1041-1049 ◽

Cited By ~ 97

Author(s):

Irfan Rahman

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Nuclear Factor Κb ◽

Alveolar Epithelial Cells ◽

Nuclear Factor ◽

Activator Protein 1 ◽

Alveolar Epithelial ◽

Factor Α ◽

Necrosis Factor

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Nuclear factor-kappaB regulates the transcription of NADPH oxidase 1 in human alveolar epithelial cells

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01464-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Weijing Wu ◽

Li Li ◽

Xiaoshan Su ◽

Zhixing Zhu ◽

Xiaoping Lin ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

A549 Cells ◽

Alveolar Epithelial Cells ◽

Nuclear Factor ◽

Alveolar Epithelial ◽

Tnf Α ◽

Potential Regulatory Role ◽

Human Alveolar Epithelial Cells

Abstract Objective Acute lung injury (ALI) is characterized by inflammation and oxidative stress. Nuclear factor-kappaB (NF-κB) mediates the expression of various inflammation-related genes, including the NADPH oxidase family. This study aimed to identify the potential regulatory role of NF-κB on NADPH oxidases in tumor necrosis factor-α (TNF-α)-induced oxidative stress in human alveolar epithelial cells. Methods A549 cells were treated with TNF-α for 24 h to establish ALI cell models. RT-PCR, western blot, assessment of oxidative stress, Alibaba 2.1 online analysis, electrophoretic mobility shift assays and luciferase reporter analysis were employed to identify the potential regulatory role of NF-κB on NADPH oxidases in TNF-α-induced oxidative stress in human alveolar epithelial cells. Results The expression of NF-κB/p65 was notably upregulated in TNF-α-stimulated A549 cells. NF-κB knockdown by siRNA significantly inhibited the TNF-α-induced oxidative stress. Moreover, NF-κB/p65 siRNA could inhibit the activation of NOX1, NOX2 and NOX4 mRNA and protein expression in TNF-α-stimulated A549 cells. The next study demonstrated that NF-κB activated the transcription of NOX1 by binding to the -261 to -252 bp (NOX1/κB2, TAAAAATCCC) region of NOX1 promoter in TNF-α-stimulated A549 cells. Conclusion Our data demonstrated that NF-κB can aggravate TNF-α-induced ALI by regulating the oxidative stress response and the expression of NOX1, NOX2 and NOX4. Moreover, NF-κB could promote the NOX1 transcriptional activity via binding its promoter in TNF-α-stimulated A549 cells.

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Friedelin Protects Against Alveolar Epithelial Cells Apoptosis in Lps-Induced Acute Pneumonia in Neonatal Rats by Suppressing NF-κB Activation

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:58-63 ◽

2020 ◽

Vol 19 (1) ◽

pp. 58-63

Author(s):

Juan Tian ◽

Tao Han ◽

Minjuan Pan

Keyword(s):

Epithelial Cells ◽

Nuclear Factor Kappa B ◽

Alveolar Epithelial Cells ◽

Nuclear Factor ◽

Neonatal Rats ◽

Alveolar Epithelial ◽

Nuclear Factor Kappa ◽

Acute Pneumonia ◽

Cellular Apoptosis

Neonatal pneumonia is caused by inflammation mediated by lipopolysaccharide from gram negative bacteria. This type of pneumonia is characterized by inflammatory and apoptotic responses. In this study, we have examined the effect of friedelin on lipopolysaccharide-induced pneumonia and the role of nuclear factor kappa B in this process. Also, using the human pulmonary alveolar epithelial cells as a model we examined the effect of lipopolysaccharide on the cell apoptosis and its protection by friedelin. The results show that friedelin prevented lipopolysaccharide-induced acute pneumonia in neonatal rats and cellular apoptosis by suppressing the nuclear factor kappa B signaling pathway. In summary, this study shows that the friedelin exhibits a remarkable protective effect on lung tissues exposed to lipopolysaccharides.

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