| Summary: | Dental pulp inflamm'ation has major clinical significance. Recent research has suggested that the fibroblast has a role as driver of the inflammatory response. The term 'neurogenic inflammation' describes the contribution of the nervous system to local inflammatory responses and is thought to play an active and dynamic role in modulating pulpal inflammation. The function of the dental pulp fibroblast in the regulation of the neurogenic response to inflammation is unknown. This thesis presents a series of experimental studies investigating the role of the fibroblast in this aspect of inflammation. Cultured human dental' pulp fibroblasts populations were used in this study using a variety of in vitro techniques. The first part of the thesis involved the detection of substance P (SP) and neuropeptide Y (NPY) receptors, NK-I and NPY-YI respectively. Results demonstrated the expression of these receptors in pulp fibroblasts both at the mRNA and protein levels and their expression levels were regulated by cytokines and neuropeptides. The second part investigated the production of neuropeptides by pulp fibroblasts lnd results showed SP expression both at the mRNA and protein levels. Tissue levels of SP and NPY were quantified and compared in healthy and carious pulps, sho~ing increased expression during dental caries. The final section examined the responsiveness of pulp fibroblasts to SP and NPY. It was shown that pulp fibroblasts increased in proliferation in response to SP and had the ability to differentiate into odontoblasts. Furthermore, pulp fibroblasts expressed osteoprotegerin (OPO) and receptor activator of nuclear factor KB ligand (RANKL) indicating a role in 'clastic' activity. The present work demonstrated a potential role of the dental pulp fibroblast in the neurogenic inflammatory response with respect to SP and NPY, leading to a clearer understanding of their role in inflammation.
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