Cytokine regulation of gingival fibroblast lysyl oxidase, collagen, and elastin

BACKGROUND: Systemic therapy with cyclosporin A, phenytoin, and nifedipine modulates cytokine levels in human gingival tissues. Functional relationships between altered cytokine levels and gingival extracellular matrix production are partially characterized. The present study investigates in cultured human gingival fibroblasts the regulation of lysyl oxidase, alpha-1 type I collagen, and elastin by selected cytokines that are elevated in drug-induced gingival overgrowth tissues. METHODS: Normal human gingival fibroblasts were cultured and then treated with selected cytokines: interleukin (IL)-1beta, IL-6, platelet-derived growth factor (PDGF)-BB, and basic fibroblast growth factor (bFGF or FGF-2). Cells were harvested at intervals, and changes in lysyl oxidase enzyme activity, and in mRNA levels of lysyl oxidase, alpha-1 type I collagen, and elastin were determined. RESULTS: bFGF reproducibly and significantly decreased human gingival fibroblast lysyl oxidase and alpha-1 type I collagen mRNA levels in a dose- and time-dependent manner; 1 nM bFGF reduced lysyl oxidase and collagen mRNA levels to 53% and to less than 10% of control after 48 hours of treatment. Interestingly, bFGF downregulated lysyl oxidase enzyme activity by 10% to 20%. IL-1, IL-6, and PDGF-BB did not significantly regulate lysyl oxidase enzyme activity, or alpha-1 type I collagen, elastin, and lysyl oxidase mRNA levels under the conditions tested. CONCLUSIONS: Previous studies have shown that modulated levels of bFGF occur in gingiva as a result of certain pharmacologic therapies. The present study suggests that modulated levels of bFGF likely influence gingival connective tissue metabolism.