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 Bacteroides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are still not fully understood.


METHODS
We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such as cell growth, protein synthesis, cell adhesion capacity, and cell cycle progression.


RESULTS
Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentrations 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 became 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 their inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, butyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 to 24 mM further result in G2/M phase arrest of GF. On the other hand, propionate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Butyrate (>2 mM) inhibited the proline-rich protein synthesis of GF. At concentrations 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 GF, the suppressive effect of propionate is less than that of butyrate. At concentration range of 4 to 24 mM, propionate suppressed the protein synthesis 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 microorganisms can contribute to the gingival tissue dysfunction and breakdown through their actions on specific biological functions of GF.
Jeng
J H
JH
Laboratory of Dental Pharmacology & Toxicology, School of Dentistry, National Taiwan University, Taipei.
Chan
C P
CP
Ho
Y S
YS
Lan
W H
WH
Hsieh
C C
CC
Chang
M C
MC
D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005232:Fatty Acids, Volatile / Q000008:administration & dosage / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005891:Gingivitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010455:Peptides / Q000187:drug effects / Q000378:metabolism; D011392:Proline / Q000187:drug effects / Q000378:metabolism; D055232:Proline-Rich Protein Domains; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013997:Time Factors
D002087:Butyrates; D005232:Fatty Acids, Volatile; D010455:Peptides; D011422:Propionates; D011506:Proteins; D003094:Collagen; D011392:Proline