The functional interaction of EGF and PDGF with bradykinin in the proliferation of human gingival fibroblasts.
Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-BB are both involved in periodontal wound healing. Each of these growth factors exerts a positive proliferative effect on cells of the periodontium in vitro. However, in vivo the peptide bradykinin is one of a complex array of mediators present in addition to these growth factors. The purposes of this investigation were to: 1) evaluate bradykinin interactions with EGF and PDGF-BB altering cell proliferation in cultured human gingival fibroblasts (HGF), periodontal ligament cells (HPDL), and cells derived from alveolar bone (HOB); and 2) determine at the signal transduction level the mechanism of interaction between EGF and bradykinin in HGF. EGF and PDGF-BB stimulated DNA synthesis in a concentration-dependent manner, as measured by [3H] thymidine incorporation. Bradykinin alone did not alter significantly based DNA synthesis values; however, bradykinin in combination with EGF reduced DNA synthesis to nearly basal levels and bradykinin in combination with PDGF reduced the DNA synthesis over 50%. Examination of the interactions between bradykinin and EGF signal transduction pathways revealed that PGE2 release was increased in the presence of bradykinin and EGF (167 +/- 33% to 317 +/- 29%). The bradykinin-stimulated PGE2 release was completely abolished by indomethacin. Indomethacin also was found to block the bradykinin inhibition of EGF-induced DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
McAllister
B S
BS
Department of Periodontology, Oregon Health Sciences University, Portland, USA.
Leeb-Lundberg
F
F
Mellonig
J T
JT
Olson
M S
MS
D000539:Alveolar Process / Q000166:cytology / Q000187:drug effects; D000077214:Becaplermin; D001920:Bradykinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D015398:Signal Transduction
D016861:Cyclooxygenase Inhibitors; D006131:Growth Inhibitors; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D005576:Colforsin; D004815:Epidermal Growth Factor; D003994:Bucladesine; D004247:DNA; D000242:Cyclic AMP; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin