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Protein kinase A enhances lipopolysaccharideinduced IL-6, IL-8, and PGE2 production by human gingival broblasts
Get PDFapplication/pdfObjective: Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal
tissues, leading to alveolar bone loss in severe clinical cases. Interleukin (IL)-6, IL-8, and the chemical mediator
prostaglandin E2 (PGE2) are known to play important roles in inflammatory responses and tissue degradation.
Recently, we reported that the protein kinase A (PKA) inhibitor H-89 suppresses lipopolysaccharide (LPS)-induced
IL-8 production by human gingival fibroblasts (HGFs). In the present study, the relevance of the PKA activity and
two PKA-activating drugs, aminophylline and adrenaline, to LPS-induced inflammatory cytokines (IL-6 and IL-8) and
PGE2 by HGFs were examined.
Methods: HGFs were treated with LPS from Porphyromonas gingivalis and H-89, the cAMP analog dibutyryl cyclic
AMP (dbcAMP), aminophylline, or adrenaline. After 24 h, IL-6, IL-8, and PGE2 levels were evaluated by ELISA.
Results: H-89 did not affect LPS-induced IL-6 production, but suppressed IL-8 and PGE2 production. In contrast,
dbcAMP significantly increased LPS-induced IL-6, IL-8, and PGE2 production. Up to 10 μg/ml of aminophylline did
not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly increased at 100 μg/ml. Similarly,
0.01 μg/ml of adrenaline did not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly
increased at concentrations of 0.1 and 1 μg/ml. In the absence of LPS, H-89, dbcAMP, aminophylline, and
adrenaline had no relevance to IL-6, IL-8, or PGE2 production.
Conclusion: These results suggest that the PKA pathway, and also PKA-activating drugs, enhance LPS-induced IL-6,
IL-8, and PGE2 production by HGFs. However, aminophylline may not have an effect on the production of these
molecules at concentrations used in clinical settings (8 to 20 μg/ml in serum). These results suggest that
aminophylline does not affect inflammatory responses in periodontal disease.journal articl
