title: Synergistic interactions of bradykinin, thrombin, interleukin 1 and tumor necrosis factor on prostanoid biosynthesis in human periodontal-ligament cells.
abstract: Prostaglandins are involved in force-induced orthodontic tooth movement. Bradykinin (BK) and thrombin are known to cause a significant time- and concentration-dependent burst of prostanoid biosynthesis in cultured human periodontal-ligament (PDL) cells. The aim now was to investigate interactive effects between interleukin 1 alpha, -beta (IL-1 alpha, -1 beta), tumour necrosis factor-alpha,-beta (TNF-alpha, -beta) and BK or thrombin on prostaglandin biosynthesis in human PDL cells. IL-1 alpha and -1 beta produced time- and concentration-dependent stimulation of prostanoid biosynthesis [prostaglandin (PG)E2 and 6-keto-PGF1alpha]. Synergistic stimulation of prostanoid biosynthesis was demonstrated when BK or thrombin were added together with IL-1 alpha or -1 beta. BK and IL-1 beta both significantly stimulated the release of [3H]arachidonic acid. No synergistic effect on [3H]arachidonic acid release was seen when BK and IL-1 beta were added simultaneously. These data suggest that the synergistic effect of BK and IL-1 beta on prostanoid biosynthesis is not due to interactions at the receptor level nor to enhanced release of arachidonic acid, but may be due to increased activity of cyclo-oxygenase. Also, TNF-alpha and -beta produced a concentration-dependent stimulation of PGE2 formation in cultured human PDL cells. Synergistic effects of BK and thrombin were demonstrated when PGE2 production was stimulated in combination with TNF-beta. In addition, a synergistic effect on the PGE2 response to IL-1 alpha or -1 beta was demonstrated when added in combination with TNF-alpha. These experiments demonstrate synergistic interactions between BK, thrombin, IL-1 and TNF on prostaglandin biosynthesis in cultured human PDL cells. The findings suggest that inflammatory mediators may act in concert in stimulating prostanoid production in response to pro-inflammatory stimuli. As an inflammatory reaction is seen in the periodontal ligament when teeth are orthodontically treated, this synergistic interaction may be of importance in force-induced tooth movement.
authors.affiliation: Department of Oral Cell Biology, University of Umeå, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ransjö
authors.forename: M
authors.initials: M
authors.lastname: Marklund
authors.forename: M
authors.initials: M
authors.lastname: Persson
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D016718:Arachidonic Acid / Q000032:analysis; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D013917:Thrombin; D015232:Dinoprostone; D001920:Bradykinin