PT  - JOURNAL ARTICLE
AU  - Mariam Bagher
AU  - Oskar Rosmark
AU  - Linda Elowsson Rendin
AU  - Annika Nybom
AU  - Sebastian Wasserström
AU  - Catharina Müller
AU  - Oskar Hallgren
AU  - Leif Bjermer
AU  - Anna-Karin Larsson-Callerfelt
AU  - Gunilla Westergren-Thorsson
TI  - PAR-2 mediated interactions between mast cells and fibroblasts cause a switch in fibroblast morphology and cytokine profile
AID  - 10.1183/13993003.congress-2019.PA2426
DP  - 2019 Sep 28
TA  - European Respiratory Journal
PG  - PA2426
VI  - 54
IP  - suppl 63
4099  - http://erj.ersjournals.com/content/54/suppl_63/PA2426.short
4100  - http://erj.ersjournals.com/content/54/suppl_63/PA2426.full
SO  - Eur Respir J2019 Sep 28; 54
AB  - Background: Protease activated receptor 2 (PAR2) is highly expressed on various cells. Although the well documented effects of PAR2 in innate immune responses to inflammation, the knowledge of PAR2 in the pathogenesis of chronic lung diseases is limited. The objective was to investigate the role of PAR2 and its effect on fibroblasts regarding changes in phenotype profile and mediator release in fibroblast monoculture and in co-culture with mast cells.Methods: The experiments were performed in 2D in vitro cultures on cell culture plastic and in a 3D ex vivo model where the cells were seeded on decellularized human lung scaffolds in order to mimic a more physiological milieu for the cells to interact. Human lung fibroblasts (HFL-1) were co-cultured with LAD2 mast cells with and without the PAR2 antagonist, P2pal-18s. The fibroblast morphology, distribution of a-smooth muscle actin protein and mediator profile were analysed.Results: The PAR-2 antagonist induced an altered fibroblast phenotype to a more elongated shape and increased aSMA expression. The PAR2 antagonist significantly induced a different mediator profile, where Il-6 (p=0.003), VEGF (p=0.004) and HGF synthesis (p=0.001) increased in fibroblasts co-cultured with mast cells. The mediators were differently synthesised when the cells were co-cultured in human lung scaffolds compared to 2D culture on plastic.Conclusions: PAR2 antagonism promote important effects on human lung fibroblast function with alterations in mediator release and morphological changes. These data indicate an important role of PAR2 in acute as well as chronic inflammatory diseases in which fibroblasts and mast cells are involved.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA2426.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).