BACKGROUND AND OBJECTIVE: Short-chain fatty acids, such as butyric acid and 
propionic acid, are metabolic by-products generated by periodontal microflora 
such as Porphyromonas gingivalis, and contribute to the pathogenesis of 
periodontitis. However, the effects of butyrate on the biological activities of 
gingival fibroblasts (GFs) are not well elucidated.
MATERIAL AND METHODS: Human GFs were exposed to various concentrations of 
butyrate (0.5-16 mm) for 24 h. Viable cells that excluded trypan blue were 
counted. Cell cycle distribution of GFs was analyzed by propidium 
iodide-staining flow cytometry. Cellular reactive oxygen species (ROS) 
production was measured by flow cytometry using 2',7'-dichlorofluorescein (DCF). 
Total RNA and protein lysates were isolated and subjected to RT-PCR using 
specific primers or to western blotting using specific antibodies, respectively.
RESULTS: Butyrate inhibited the growth of GFs, as indicated by a decrease in the 
number of viable cells. This event was associated with an induction of G0/G1 and 
G2/M cell cycle arrest by butyrate (4-16 mm) in GFs. However, no marked 
apoptosis of GFs was noted in this experimental condition. Butyrate (> 2 mm) 
inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the 
levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT-PCR 
and western blotting, respectively. This toxic effect of butyrate was associated 
with the production of ROS.
CONCLUSION: These results suggest that butyrate generated by periodontal 
pathogens may be involved in the pathogenesis of periodontal diseases via the 
induction of ROS production and the impairment of cell growth, cell cycle 
progression and expression of cell cycle-related genes in GFs. These events are 
important in the initiation and prolongation of inflammatory processes in 
periodontal diseases.