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Role of Intercellular Interactions between Mast Cells and Gingival Fibroblasts in Mediating Inflammation

The mechanisms that mediate acute exacerbations in chronic inflammatory diseases such as periodontitis are not understood. IL-8 is a potent chemoattractant for neutrophils in acute inflammatory lesions. We investigated the role of fibroblast-mast cell interactions on short-term IL-8 release. Human gingival fibroblasts were co-cultured with human mast cells (HMC-1). After co-culture, the concentration of IL-8 was measured by ELISA. HMC co-cultured with fibroblasts increased IL-8 secretion by >6-fold, which required intercellular contact and was blocked by the gap junction inhibitor BGA. Thapsigargin-induced elevations of intracellular calcium increased IL-8 levels by 15-fold. Chemotaxis of human neutrophils was significantly enhanced in response to conditioned medium from co-cultures. Calcein-dye transfer showed intercellular, gap junction communication between HMC and fibroblasts that was dependent in part on β1 integrins. We conclude that mast cells adhere to fibroblasts and promote IL-8 secretion, thereby enhancing neutrophil chemotaxis and possibly the perpetuation of the inflammatory response.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31463
Date20 December 2011
CreatorsTermei, Reza
ContributorsMcCulloch, Christopher
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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