Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2
(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.
(Less)
- author
- Bagher, Mariam
LU
; Larsson-Callerfelt, Anna Karin
LU
; Rosmark, Oskar LU
; Hallgren, Oskar LU ; Bjermer, Leif LU and Westergren-Thorsson, Gunilla LU
- organization
- publishing date
- 2018-09-15
- 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
- article number
- 59
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:30219079
- 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
- 2024-05-27 18:49:58
@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 < 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.</p>}}, author = {{Bagher, Mariam and Larsson-Callerfelt, Anna Karin and Rosmark, Oskar and Hallgren, Oskar and Bjermer, Leif and Westergren-Thorsson, Gunilla}}, issn = {{1478-811X}}, keywords = {{Human lung fibroblast; Lung; Mast cell; Migration; Protease activated receptor 2; Tryptase}}, language = {{eng}}, month = {{09}}, number = {{1}}, publisher = {{BioMed Central (BMC)}}, 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}}, doi = {{10.1186/s12964-018-0269-3}}, volume = {{16}}, year = {{2018}}, }