The functional interaction of EGF and PDGF with bradykinin in the proliferation of human gingival fibroblasts
The aim of this study was to investigate the interactions of epidermal growth factor (EGF) and platelet-derived growth factor-BB (PDGF-BB) with the inflammatory mediator bradykinin. Gingival, bone, and periodontal ligament explants were taken from healthy patients. Cells were incubated and DNA synthesis was determined by [3H] thymidine incorporation. RIA was employed to assay PGE2 in the samples. Bradykinin alone did not significantly alter basal DNA synthesis values. EGF and PDGF-BB-induced DNA synthesis were found to be concentration dependent. The addition of 100 nM bradykinin inhibited growth-factor-induced DNA synthesis, even at elevated concentrations of GF. Bradykinin and EGF reduced DNA synthesis nearly to basal levels. Bradykinin and PDGF-BB reduced DNA synthesis over 50%. Cells stimulated with bradykinin released PGE2. This release was potentiated when bradykinin was added in combination with EGF. Indomethacin blocked the release of PGE2. Pre-treatment with indomethacin completely blocked the bradykininstimulated release of PGE2. Bradykinin may be a negative modulator of early proliferative response in mesenchymal cells of the periodontium during wound healing. Determining the precise mechanism of bradykinin inhibition for growth-factor-induced DNA synthesis is essential for the development of a potential therapeutic approach to control the reported bradykinin inhibition. Examination of the potential interactions between EFG and bradykinin at the signal transduction level has revealed that the primary point of interaction appears to be through the release of PGE2. Bradykinin has been shown to stimulate the rapid synthesis and release of PGE2, and the presence of EGF actually seems to enhance this release. In conclusion, EGF- and PDGF-induced proliferative responses are inhibited by bradykinin in cells of the periodontium. This mechanism appears to be mediated by PGE2 through a cAMP-dependent pathway. [c.c.]
McAllister, B., F. Leeb-Lundberg, J. Mellonig, and M. Olson, J Periodont, 66:429,1995