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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/31463 |
| Date | 20 December 2011 |
| Creators | Termei, Reza |
| Contributors | McCulloch, Christopher |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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