title: Intercellular interactions between mast cells and fibroblasts promote pro-inflammatory signaling.
abstract: The mechanisms that mediate acute exacerbations in chronic inflammatory diseases are not understood. As IL-8 is a potent chemoattractant for neutrophils in acute inflammatory lesions, we investigated the role of fibroblast-mast cell interactions in short-term IL-8 release. Human gingival fibroblasts were co-cultured with human mast cells (HMC). The concentration of IL-8 in co-culture medium was measured by ELISA. HMC-fibroblast co-cultures showed >8-fold higher IL-8 secretion than fibroblasts or HMC alone. Increased IL-8 secretion required HMC-fibroblast intercellular contact, was enhanced by serum and was blocked by the gap junction inhibitor β-glycyrrhetinic. Calcein-dye transfer showed intercellular, gap junction communication between HMC and fibroblasts that was dependent in part on hyaluronic acid on the cell surface of fibroblasts. IL-8 secretion by fibroblasts was strongly promoted by hyaluronic acid. Pre-treatment of HMC with thapsigargin provoked 15-fold higher IL-8 production by fibroblasts in co-cultures. Chemotaxis of mouse neutrophils was enhanced 2-fold in response to conditioned medium from HMC-fibroblast co-cultures. We conclude that mast cells adhere to fibroblasts and promote IL-8 secretion, which enhances neutrophil chemotaxis and the inflammatory response.
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Room 244, Fitzgerald Building, 150 College Street, Toronto, ON, Canada M5S 3E2.
authors.forename: R
authors.initials: R
authors.lastname: Termei
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Room 244, Fitzgerald Building, 150 College Street, Toronto, ON, Canada M5S 3E2.
authors.forename: C
authors.initials: C
authors.lastname: Laschinger
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Room 244, Fitzgerald Building, 150 College Street, Toronto, ON, Canada M5S 3E2.
authors.forename: W
authors.initials: W
authors.lastname: Lee
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Room 244, Fitzgerald Building, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: christopher.mcculloch@utoronto.ca.
authors.forename: C A
authors.initials: CA
authors.lastname: McCulloch
mesh_terms: D000293:Adolescent; D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis; D002648:Child; D005347:Fibroblasts / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D055571:Secretory Pathway; D015398:Signal Transduction
chemical_list: C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D006820:Hyaluronic Acid; D006034:Glycyrrhetinic Acid