title: Cross-talk between human mast cells and bronchial epithelial cells in plasminogen activator inhibitor-1 production via transforming growth factor-β1.
abstract: Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC-epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1-mediated activation pathway.
authors.affiliation: 1 Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Seong H
authors.initials: SH
authors.lastname: Cho
authors.forename: Sun H
authors.initials: SH
authors.lastname: Lee
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.forename: Marianna
authors.initials: M
authors.lastname: Kulka
authors.forename: Soon C
authors.initials: SC
authors.lastname: Shin
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002460:Cell Line; D053818:Chymases / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D058258:Serpin E2 / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D058258:Serpin E2; C511869:Serpine2 protein, mouse; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D007073:Immunoglobulin E; D053818:Chymases
keywords: chymase; epithelial cells; mast cells; plasminogen activator inhibitor-1; transforming growth factor-β1