scholarly journals Tumor Necrosis Factor-α in Airway Secretions from Cystic Fibrosis Patients Upregulate Endothelial Adhesion Molecules and Induce Airway Epithelial Cell Apoptosis: Implications for Cystic Fibrosis Lung Disease

2008 ◽  
Vol 21 (4) ◽  
pp. 851-865 ◽  
Author(s):  
S. Mitola ◽  
V. Sorbello ◽  
E. Ponte ◽  
E. Copreni ◽  
C. Mascia ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Adhesion Molecules ◽  
Acute Exacerbation ◽  
Adhesion Molecule ◽  
Crucial Role ◽  
Adhesion Molecule Expression ◽  
Airway Epithelial ◽  
Tnf Α ◽  
Endothelial Adhesion Molecules

Airway inflammation plays a crucial role in lung damage in cystic fibrosis (CF) and is characterized by a persistent influx of neutrophils into the airways. We hypothesized that the high levels of inflammatory products that accumulate in the microenvironment of the CF lung contribute to induce the persistent neutrophil recruitment and the airway epithelial damage. Thus, we evaluated the in vitro effect of sputum sol phase (SSP) from CF patients on a) adhesion molecule expression by human microvascular endothelial cells (HMECs) and b) apoptosis of human bronchial epithelial cells (HBECs), both wild-type and CFTR-defective. SSP was obtained from 7 clinically stable adult CF patients and 8 patients with an acute exacerbation. HMECs and HBECs were cultured in the absence or presence of SSP. Cell adhesion molecule expression was assessed by flow cytometry and cell death by the detection of histone-associated DNA fragments, caspase activation, and cytochrome c release. SSP obtained from CF patients, especially at the time of an acute exacerbation, induced a) an upregulation of endothelial adhesion molecules on cultured HMECs that was associated with an increase of neutrophil adhesion to these cells, and was mediated at least in part by TNF-α and IL-1 and b) apoptosis of airway epithelial cells, mainly activated by TNF-α pathway. These results suggest that the high concentrations of inflammatory mediators in CF airways contribute both to the chronic neutrophil influx and the airway damage, and support the crucial role of early anti-inflammatory treatment in the disease.

TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

2003 ◽  
Vol 284 (2) ◽  
pp. C422-C428 ◽  
Author(s):  
Makoto Sasaki ◽  
D. Ostanin ◽  
J. W. Elrod ◽  
T. Oshima ◽  
P. Jordan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Nadph Oxidase ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Tnf Α ◽  
Oxidase Inhibition ◽  
Endothelial Adhesion Molecules ◽  
Cytochrome P 450

It is strongly suspected that cytokine-induced gene expression in inflammation is oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-α, trigger gene expression of endothelial adhesion molecules including mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role in gut inflammation by governing the infiltration of leukocytes into the intestine. Several groups suggest that endothelial-derived reduced NADP (NADPH) oxidase produces signaling oxidants that control the expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1). In addition to NADPH oxidase, cytochrome P-450 (CYP450) monooxygenases have also been shown to trigger cytokine responses. We found that in high endothelial venular cells (SVEC4-10), multiple inhibitors of CYP450 monooxygenases (SKF-525a, ketoconazole, troleandomycin, itraconazole) attenuated TNF-α induction of MAdCAM-1, whereas NADPH oxidase inhibition (PR-39) did not. Conversely, E-selectin, ICAM-1, and VCAM-1 induction requires both NADPH oxidase and CYP450-derived oxidants. We show here that MAdCAM-1 induction may depend exclusively on CYP450-derived oxidants, suggesting that CYP450 blockers might represent a possible novel therapeutic treatment for human IBD.

Expression of soluble endothelial adhesion molecules in clinical cardiopulmonary bypass

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 314-321 ◽  
Author(s):  
Joseph Galea ◽  
Naomi Rebuck ◽  
Adam Finn ◽  
Alex Manché ◽  
Neil Moat
Keyword(s):  
Cardiopulmonary Bypass ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Control Group ◽  
Adhesion Molecule Expression ◽  
Endothelial Cell Activation ◽  
Endothelial Adhesion Molecule ◽  
Endothelial Adhesion Molecules ◽  
Serial Measurements

Soluble endothelial adhesion molecule expression in clinical cardiopulmonary bypass (CPB) was investigated. Neutrophil-mediated endothelial injury plays an important role in CPB-induced organ dysfunction. The adhesion of neutrophil to the endothelium is central to this process. It has been well documented that CPB induces neutrophil activation and changes in neutrophil adhesion molecule expression, but the effect of CPB on endothelial cell activation is not known. This study was designed to measure soluble endothelial adhesion molecules during CPB. We made serial measurements (by specific enzyme-linked immunoabsorbent assay) of plasma levels of the soluble endothelial adhesion molecules, ICAM-1 and E-selectin in patients undergoing routine CPB ( n =7) and in a control group (thoracotomy, n = 3). The results show an initial significant decrease during CPB followed by an increase in plasma E-selectin from 29.3 ± 5.1 ng/ml (mean ± SEM) prebypass to 34.0 ± 5.4 ng/ml at 48 h postbypass. Likewise, plasma ICAM-1 significantly decreased during CPB and then increased from 246.3 ± 38.0 ng/ml before bypass to 324.8 ± 25.0 ng/ml and 355.0 ± 23.0 ng/ml at 24 and 48 h after bypass, respectively. The rise in levels is statistically significant ( p < 0.05). This study shows a decrease in circulating ICAM-1 and soluble E-selectin during CPB and an increase in their levels at 48 h after CPB.

scholarly journals Ozone effect on inflammatory and proteomic profile of human macrophages and airway epithelial cells

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
L Falcone ◽  
E Aruffo ◽  
P Di Carlo ◽  
P Del Boccio ◽  
M C Cufaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Air Pollution ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Urban Areas ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Proteomics Analysis ◽  
Human Macrophages ◽  
Tnf Α

Abstract Background Reactive oxygen species (ROS) and oxidative stress in the respiratory system are involved in lung inflammation and tumorigenesis. Ozone (O3) is one of the main components of air pollution in urban areas able to act as strong pro-oxidant agent, however its effects on human health is still poorly investigated. In this study the effect of O3 has been evaluated in THP-1 monocytes differentiated into macrophages with PMA and in HBEpC (primary human bronchial epithelial) cells, two model systems for in vitro studies and translational research. Methods Cell viability, ROS and pro-inflammatory cytokines like interleukin-8(IL-8) and tumor necrosis factor(TNF-α) have been tested in the above-mentioned cell lines not exposed to any kind of pollution (basal condition-b.c.) or exposed to O3 at a concentration of 120 ppb. In HBEpC a labelfree shotgun proteomics analysis has been also performed in the same conditions. Results Ozone significantly increased the production of IL-8 and TNF-α in THP-1 whereas no changes were shown in HBEpC. In both cell lines lipopolysaccharide(LPS) caused an increase of IL-8 and TNF-α production in b.c. and O3 treatment potentiated this effect. Ozone exposure increased ROS formation in a time dependent manner in both cell lines and in THP-1 cells a decrease in catalase activity was also shown. Finally, according to these data, functional proteomics analysis revealed that in HBEpC exposure to O3 many differential proteins are related to oxidative stress and inflammation. Conclusions Our results indicate that O3, at levels that can be reached in urban areas, causes an increase of pro-inflammatory agents either per se or potentiating the effect of immune response stimulators in cell models of human macrophages and human airway epithelial cells. Interestingly, the proteomic analysis showed that besides the dysregulated proteins, O3 induced the expression of AKR1D1 and AKR1B10, proteins recognized to play a significant role in cancer development. Key messages This study adds new pieces of information on the association between O3 exposure and detrimental effects on respiratory system. This study suggests the need for further research on the mechanisms involved and for a continued monitoring/re-evaluation of air pollution standards aimed at safeguarding human health.

Differential expression of ORCC and CFTR induced by low temperature in CF airway epithelial cells

1995 ◽  
Vol 268 (1) ◽  
pp. C243-C251 ◽  
Author(s):  
M. E. Egan ◽  
E. M. Schwiebert ◽  
W. B. Guggino
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Incubation Temperature ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Channel Activity ◽  
Patch Clamp Recording ◽  
Cl Channel ◽  
Channel Expression

When nonepithelial cell types expressing the delta F508-cystic fibrosis transmembrane conductance regulator (CFTR) mutation are grown at reduced temperatures, the mutant protein can be properly processed. The effect of low temperatures on Cl- channel activity in airway epithelial cells that endogenously express the delta F508-CFTR mutation has not been investigated. Therefore, we examined the effect of incubation temperature on both CFTR and outwardly rectifying Cl- channel (ORCC) activity in normal, in cystic fibrosis (CF)-affected, and in wild-type CFTR-complemented CF airway epithelia with use of a combination of inside-out and whole cell patch-clamp recording, 36Cl- efflux assays, and immunocytochemistry. We report that incubation of CF-affected airway epithelial cells at 25-27 degrees C is associated with the appearance of a protein kinase A-stimulated CFTR-like Cl- conductance. In addition to the appearance of CFTR Cl- channel activity, there is, however, a decrease in the number of active ORCC when cells are grown at 25-27 degrees C, suggesting that the decrease in incubation temperature may be associated with multiple alterations in ion channel expression and/or regulation in airway epithelial cells.

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