Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts

Background: Various periodontal and root canal pathogens, such as the Bacte roides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are st ill not fully understood. Methods: We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such a s cell growth, protein synthesis, cell adhesion capacity, and cell cycle pr ogression. Results: Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentr ations of 4, 8, and 16 mM, butyrate suppressed the cell growth by 11 to 58% , 16 to 60%, and 50 to 71%, respectively. The response of cultured gingival fibroblasts to SCFA showed individual differences. Morphologically, GF bec ame larger and more flattened in appearance following exposure to butyrate (>8 mM) and propionate (>24 mM) for 5 days. Inhibitory effects of butyrate (>2 mM) and propionate (>8 mM) on the growth of GF were due possibly to the ir inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, b utyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 t o 24 mM further result in G2/M phase arrest of GF. On the other hand, propi onate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Buty rate (>2 mM) inhibited the proline-rich protein synthesis of GE At concentr ations of 4, 8, 16, and 24 mM, butyrate inhibited the protein synthesis of HGF-1 by 42%, 43%, 51%, and 54%, respectively. In all strains of cultured G F, the suppressive effect of propionate is less than that of butyrate. At c oncentration range of 4 to 24 mM, propionate suppressed the protein synthes is of HGF-1 by 23 to 43%. However, both butyrate and propionate (4 to 48 mM ) exerted little effects on the adhesion of GF to type I collagen within 3 hours of incubation. Conclusions: These results suggested that SCFA released by pathogenic micro organisms can contribute to the gingival tissue dysfunction and breakdown t hrough their actions on specific biological functions of GF.