Bradykinin is a potent inflammatory mediator which has been implicated in both chronic inflammatory conditions, such as periodontal disease and rheumatoid arthritis, as well as in acute inflammatory conditions like anaphalacitic reactions and normal surgical wound healing. Several specific responses of bradykinin which are well characterized include vacillation, increased permeability, vascular smooth muscle relaxation/contraction and pain. However, the influences of bradykinin on normal connective tissue cells and the mechanisms of signal transduction are much less understood. The overall objective of this research proposal is to elucidate the signaling pathways for bradykinin and to use this knowledge to determine the mechanisms by which bradykinin interacts with specific growth factors. Hence, the specific experimental aims to test the outlined hypotheses and to meet the overall project objective are as follows: I. To determine the basic binding parameters of the bradykinin receptor in cultured gingival fibroblasts and to determine the nature of bradykinin signal transduction in gingival fibroblasts, osteoblasts and periodontal ligament fibroblasts. II. To characterize the bradykinin induced eicosanoid release in gingival fibroblasts and to examine bradykinin in combination with the growth factors EGF and PDGF. III. To examine the influences of bradykinin on the growth factor induced DNA synthesis and to study the mechanisms of this interaction. IV. To investigate osteogenin, a growth factor like mediator, for differential signaling in the cells of the periodontium and to determine the interactions with bradykinin. V. To determine the role PAF plays, with respect to bradykinin production and action, in the PMN as well as in gingival fibroblasts, osteoblasts and periodontal ligament cells.
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