Cross-Talk between Human Mast Cells and Bronchial Epithelial Cells in Plasminogen Activator Inhibitor-1 Production via Transforming Growth Factor-β1

Lee, Sun H.; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon Cheon; Schleimer, Robert P.

doi:10.1165/rcmb.2013-0399oc

Cited by 27 publications

(23 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TGF-β-inducible gene PAI-1 (plasminogen activator inhibitor-1) was used as a consistent marker for TGF-β activity. Inhibition of ALK5 attenuated the RSV-induced mRNA expression of PAI-1 in BEAS-2B cells [54]. Moreover, PAI-1 can also be induced by GC in different cell types [55, 56].…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

et al. 2017

View full text Add to dashboard Cite

Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-β (TGF-β) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-β. In the current study, we examine the contribution of TGF-β activity to the GC-resistance caused by viral infection. We demonstrate that viral infection of human bronchial epithelial cells with RSV, RV or IAV impairs GC anti-inflammatory action. Poly(I:C), a synthetic analog of double-stranded RNA, also impairs GC activity. Both viral infection and poly(I:C) increase TGF-β expression and activity. Importantly, the GC impairment was attenuated by the selective ALK5 (TGFβRI) inhibitor, SB431542 and prevented by the therapeutic agent, tranilast, which reduced TGF-β activity associated with viral infection. This study shows for the first time that viral-induced glucocorticoid-insensitivity is partially mediated by activation of endogenous TGF-β.

show abstract

Section: Resultsmentioning

confidence: 99%

Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

et al. 2017

View full text Add to dashboard Cite

show abstract

“…It is possible that the use of agents such as inhibitors of PAI-1 may be of utility in subjects with fibrotic EoE. In addition, since PAI-1 can be made by mast cells where it is induced by chymase-activated TGFβ1 (22), it will be of interest to see what role inflammation does play in PAI-1 expression in EoE.…”

Section: Discussionmentioning

confidence: 99%

“…PAI-1 overexpression, triggered by viruses and allergens, is associated with airway fibrosis while PAI-1 deficiency protects mice from fibrotic airway remodeling (21, 23–26, 29). Mast cell derived TGFβ1 increases PAI-1 expression from immortalized airway epithelial cells in culture (22). In addition, a single nucleotide polymorphism 4G in the PAI-1 gene associates with human asthma risk (27, 28).…”

Section: Introductionmentioning

confidence: 99%

TGF-β1–induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis

Rawson

Yang

Newbury

et al. 2016

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Background Eosinophilic esophagitis is an allergic disease of increasing worldwide incidence. Complications are due to tissue remodeling and involve transforming growth factor-β1 (TGFβ1) mediated fibrosis. Plasminogen Activator Inhibitor-1 (PAI-1/serpinE1) can be induced by TGFβ1 but its role in EoE is not known. Objective To understand the expression and role of PAI-1 in EoE. Methods We used esophageal biopsy specimens and plasma samples from control and EoE subjects, primary human esophageal epithelial cells, and EoE fibroblasts in immunohistochemistry, quantitative PCR, and immunoassay experiments to understand the induction of PAI-1 by TGFβ1, the relationship between PAI-1 and esophageal fibrosis, and the role of PAI-1 in fibrotic gene expression. Results PAI-1 expression was significantly elevated in epithelial cells of active EoE biopsies as compared with inactive EoE or control biopsies (p<0.001). Treatment of primary esophageal epithelial cells with recombinant TGFβ1 increased PAI-1 transcription, intracellular protein expression, and secretion. Esophageal PAI-1 expression correlated with basal zone hyperplasia, a fibrosis, and markers of esophageal remodeling including vimentin, TGFβ1, collagen I, fibronectin, and matrix metalloproteases and plasma PAI-1 levels correlated with plasma TGFβ1. PAI-1 inhibition significantly decreased baseline and TGFβ1-induced fibrotic gene expression. Conclusions PAI-1 is significantly elevated in the EoE epithelium, reflects fibrosis, and its inhibition decreases TGFβ1-induced gene expression. Epithelial PAI-1 may serve as a marker of EoE severity and form part of a TGFβ1-induced pro-fibrotic network.

show abstract

“…A range of functions demonstrated would be consistent with these proteases contributing to inflammation and tissue remodelling. Thus, tryptase can interact with various cell types, induce collagen secretion by fibroblasts, act as a growth factor for fibroblasts, airway smooth muscle and epithelial cells, can stimulate release of cytokines from epithelial, endothelial and airway smooth muscle cells and can itself provoke MC degranulation . MC chymase can cleave and activate matrix metalloproteinase (MMP‐1, 2, 3 and 9), control the bioavailability of various cytokines and convert angiotensin I to angiotensin II .…”

Section: Introductionmentioning

confidence: 99%

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

Zhou

Wei

Cox

et al. 2018

Allergy

View full text Add to dashboard Cite

Background: An increased degree of mast cell (MC) degranulation and damage to the epithelial lining are prominent features of bronchial asthma. In asthmatic airways, it seems likely that epithelial cells will be exposed to increased concentrations of proteases from MC, though their actions on the epithelium are still not very clear. Methods: Bronchial rings from human lung tissue or 16HBE cell monolayer were incubated with MC chymase in different doses or various inhibitors. The sections of paraffin-embedded tissue were haematoxylin-eosin stained and computerized by image analysis for epithelial damage-scale-evaluation; the cell viability, proliferation, adhesion and lactate dehydrogenase activity release were assayed; the expressions of gelatinases, cell junction molecules and structure proteins of 16HBE were examined. Results: Mast cell chymase was found to provoke profound changes in the morphology of bronchi epithelial layer. Following incubation with chymase, there was 40% reduction in the length of epithelium that was intact, with detachment of columnar epithelial cells and basal cells. Chymase reduced epithelial cell proliferation and induced cell detachment, which were associated with the changes in secretion and activation of matrix metalloproteinase-2/9. In intact epithelial cell layers, immunocytochemistry study revealed that chymase reduced the expressions of occludin, claudin-4, ZO-1, E-cadherin, focal adhesion kinase and cytokeratin. Overall data of this study indicated that MC chymase can influence tissue remodelling, disrupt epithelial cell junctions, inhibit wound healing and impair the barrier function of epithelium, resulting in dysfunction of airway wall and ECM remodelling in pathogenesis of asthma. Conclusion: Mast cell chymase plays a key role in inducing the damage to bronchial epithelium in asthma. K E Y W O R D S bronchial epithelium,

show abstract

Cross-Talk between Human Mast Cells and Bronchial Epithelial Cells in Plasminogen Activator Inhibitor-1 Production via Transforming Growth Factor-β1

Cited by 27 publications

References 52 publications

Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

TGF-β1–induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis

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

Contact Info

Product

Resources

About