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Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2

Bagher, Mariam LU ; Larsson-Callerfelt, Anna Karin LU ; Rosmark, Oskar LU ; Hallgren, Oskar LU ; Bjermer, Leif LU and Westergren-Thorsson, Gunilla LU (2018) In Cell Communication and Signaling 16(1).
Abstract

Background: Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation. Methods: Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or... (More)

Background: Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation. Methods: Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts and mast cells. Results: The migratory capacity of HFL-1 cells was enhanced by blood-derived mast cells (p < 0.02), LAD2 cells (p < 0.001), conditioned medium (p < 0.05) and tryptase (p < 0.006). P2pal-18S decreased the induced migration caused by mast cells (p < 0.001) and tryptase (p < 0.001) and the expression of PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with IgE/Anti IgE had no further effects on fibroblast migration. Conclusions: Mast cells and the mast cell mediator tryptase may have crucial roles in inducing lung fibroblast migration via PAR-2 activation, which may contribute to remodeling processes in chronic lung diseases.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Human lung fibroblast, Lung, Mast cell, Migration, Protease activated receptor 2, Tryptase
in
Cell Communication and Signaling
volume
16
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85053433505
ISSN
1478-811X
DOI
10.1186/s12964-018-0269-3
language
English
LU publication?
yes
id
68b4f46b-566d-4704-8b89-78d9b53ee638
date added to LUP
2018-10-11 09:00:13
date last changed
2019-04-10 04:14:52
@article{68b4f46b-566d-4704-8b89-78d9b53ee638,
  abstract     = {<p>Background: Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation. Methods: Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts and mast cells. Results: The migratory capacity of HFL-1 cells was enhanced by blood-derived mast cells (p &lt; 0.02), LAD2 cells (p &lt; 0.001), conditioned medium (p &lt; 0.05) and tryptase (p &lt; 0.006). P2pal-18S decreased the induced migration caused by mast cells (p &lt; 0.001) and tryptase (p &lt; 0.001) and the expression of PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with IgE/Anti IgE had no further effects on fibroblast migration. Conclusions: Mast cells and the mast cell mediator tryptase may have crucial roles in inducing lung fibroblast migration via PAR-2 activation, which may contribute to remodeling processes in chronic lung diseases.</p>},
  articleno    = {59},
  author       = {Bagher, Mariam and Larsson-Callerfelt, Anna Karin and Rosmark, Oskar and Hallgren, Oskar and Bjermer, Leif and Westergren-Thorsson, Gunilla},
  issn         = {1478-811X},
  keyword      = {Human lung fibroblast,Lung,Mast cell,Migration,Protease activated receptor 2,Tryptase},
  language     = {eng},
  month        = {09},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Cell Communication and Signaling},
  title        = {Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2},
  url          = {http://dx.doi.org/10.1186/s12964-018-0269-3},
  volume       = {16},
  year         = {2018},
}