Modulation of gingival fibroblast minocycline accumulation by biological mediators.
Gingival fibroblasts actively accumulate tetracyclines, thereby enhancing their redistribution from blood to gingiva. Since growth factors and pro-inflammatory cytokines regulate many fibroblast activities, they could potentially enhance fibroblast minocycline accumulation. To test this hypothesis, we treated gingival fibroblast monolayers for 1 or 6 hours with platelet-derived growth factor-BB (PDGF), fibroblast growth factor-2 (FGF), transforming growth factor-beta1 (TGF), or tumor necrosis factor-alpha (TNF). Minocycline uptake was assayed at 37 degrees by a fluorescence method. All 4 factors significantly enhanced minocycline uptake (P < or = 0.008, ANOVA), primarily by increasing the affinity of transport. Treatment for 6 hours with 10 ng/mL FGF, PDGF, TGF, or TNF enhanced fibroblast minocycline uptake by 19% to 25%. Phorbol myristate acetate enhanced fibroblast minocycline uptake by 28%, suggesting that protein kinase C plays a role in up-regulating transport. These effects on transport provide a mechanism by which systemic tetracyclines could be preferentially distributed to gingival wound or inflammatory sites.
Walters
J D
JD
Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, PO Box 182357, Columbus, OH 43218-2357, USA. walters.2@osu.edu
Nakkula
R J
RJ
Maney
P
P
D000328:Adult; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects*; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008911:Minocycline / Q000493:pharmacokinetics*; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
D000900:Anti-Bacterial Agents; D006133:Growth Substances; D011493:Protein Kinase C; D008911:Minocycline; D013755:Tetradecanoylphorbol Acetate