Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells

Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.

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Stimulation of both human bronchial epithelium and neutrophils is needed for maximal interactive adhesion

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.1.l80 ◽

1996 ◽

Vol 270 (1) ◽

pp. L80-L87 ◽

Cited By ~ 5

Author(s):

P. G. Bloemen ◽

M. C. Van den Tweel ◽

P. A. Henricks ◽

F. Engels ◽

M. J. Van de Velde ◽

...

Keyword(s):

Epithelial Cells ◽

Cultured Cells ◽

Bronchial Epithelium ◽

Bronchial Epithelial Cells ◽

Intercellular Adhesion Molecule ◽

Tnf Alpha ◽

Epithelial Cell Line ◽

Ifn Gamma ◽

Bronchial Epithelial ◽

Stimulation Of

It has become clear that the bronchial epithelium is not just a passive barrier but plays an active role in inflammation. It can produce several inflammatory mediators and does express cell adhesion molecules of which intercellular adhesion molecule (ICAM)-1 can be upregulated by cytokines like interferon (IFN)-gamma. In the present study, we analyzed in detail the interaction of neutrophils with human bronchial epithelial cells, both primary cultured cells and the bronchial epithelial cell line BEAS-2B. Confluent monolayers of epithelial cells were incubated with freshly isolated 51Cr-labeled neutrophils for 30 min at 37 degrees C; then the nonadherent cells were removed by washing gently. Stimulation of the epithelial cells with IFN-gamma or the combination of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) (which doubles the ICAM-1 expression) increased neutrophil adhesion. Activation of the neutrophils themselves with N-formylmethionyl-leucyl-phenylalanine (fMLP), platelet-activating factor, or TNF-alpha also caused a profound enhancement of the adhesion. A significant additional increase was found when the epithelial cells had been exposed to IFN-gamma and the neutrophils were stimulated with fMLP simultaneously. This effect was even more pronounced with epithelium preincubated with IFN-gamma and TNF-alpha. With the use of monoclonal antibodies against CD18 and ICAM-1, it was demonstrated that the increased adhesion was mainly mediated by the ICAM-1/beta 2-integrin interaction. This study highlights that both the activation state of the bronchial epithelial cells and the activation state of the neutrophils are critical for their interactive adhesion.

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Identification of domains in apoA-I susceptible to proteolysis by mast cell chymase: implications for HDL function

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)32040-x ◽

2000 ◽

Vol 41 (6) ◽

pp. 975-984

Author(s):

Miriam Lee ◽

Patrizia Uboldi ◽

Daniela Giudice ◽

Alberico L. Catapano ◽

Petri T. Kovanen

Keyword(s):

Mast Cell ◽

Hdl Function ◽

Mast Cell Chymase

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Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF-κB-mediated survival signaling☆

Experimental Cell Research ◽

10.1016/j.yexcr.2005.12.033 ◽

2006 ◽

Vol 312 (8) ◽

pp. 1289-1298 ◽

Cited By ~ 35

Author(s):

M LESKINEN ◽

H HEIKKILA ◽

M SPEER ◽

J HAKALA ◽

M LAINE ◽

...

Keyword(s):

Mast Cell ◽

Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Cell Apoptosis ◽

Survival Signaling ◽

Muscle Cell Apoptosis ◽

Mast Cell Chymase

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Regulation of extravascular coagulation and fibrinolysis by heparin‐dependent mast cell chymase

The FASEB Journal ◽

10.1096/fj.01-0486fje ◽

2001 ◽

Vol 15 (14) ◽

pp. 1-25 ◽

Cited By ~ 28

Author(s):

Elena Tchougounova ◽

Gunnar Pejler

Keyword(s):

Mast Cell ◽

Mast Cell Chymase ◽

Coagulation And Fibrinolysis

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Effect of mast cell chymase inhibitor on the development of scleroderma in tight-skin mice

British Journal of Pharmacology ◽

10.1038/sj.bjp.0706209 ◽

2005 ◽

Vol 145 (4) ◽

pp. 424-431 ◽

Cited By ~ 32

Author(s):

Naotaka Shiota ◽

Eiichi Kakizoe ◽

Keiko Shimoura ◽

Tetsuya Tanaka ◽

Hideki Okunishi

Keyword(s):

Mast Cell ◽

Tight Skin ◽

Mast Cell Chymase ◽

Chymase Inhibitor

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Expression of lipocortins in human bronchial epithelial cells: effects of IL-1β , TNF-α, LPS and dexamethasone

Mediators of Inflammation ◽

10.1155/s0962935196000300 ◽

1996 ◽

Vol 5 (3) ◽

pp. 210-217

Author(s):

M. M. Verheggen ◽

H. I. M. de Bont ◽

P. W. C. Adriaansen-Soeting ◽

B. J. A. Goense ◽

C. J. A. M. Tak ◽

...

Keyword(s):

Epithelial Cells ◽

Bronchial Epithelium ◽

Northern Blotting ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Annexin I ◽

Tnf Α

In this study, we investigated the expression of lipocortin I and II (annexin I and I in the human bronchial epithelium, bothin vivoandin vitro. A clear expression of lipocortin I and II protein was found in the epithelium in sections of bronchial tissue. In cultured human bronchial epithelial cells we demonstrated the expression of lipocortin I and II mRNA and protein using Northern blotting, FACScan analysis and ELISA. No induction of lipocortin I or II mRNA or protein was observed after incubation with dexamethasone. Stimulation of bronchial epithelial cells with IL-1β, TNF-α or LPS for 24 h did not affect the lipocortin I or II mRNA or protein expression, although PGE2and 6-keto-PGF1αproduction was significantly increased. This IL-1β- and LPS-mediated increase in eicosanoids could be reduced by dexamethasone, but was not accompanied by an increase in lipocortin I or II expression. In human bronchial epithelial cells this particular glucocorticoid action is not mediated through lipocortin I or II induction.

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