RRC ID 51957
Author Shirasugi M, Nishioka K, Yamamoto T, Nakaya T, Kanamura N.
Title Normal human gingival fibroblasts undergo cytostasis and apoptosis after long-term exposure to butyric acid.
Journal Biochem Biophys Res Commun
Abstract The causes of periodontal disease are complex. Butyric acid, a metabolite of periodontopathic bacteria such as Porphyromonas gingivalis, acts as a histone deacetylase inhibitor that has a direct effect on mRNA expression. Butyric acid produced by Clostridium butyricum in the intestinal tract induces differentiation of regulatory T cells, thereby suppressing inflammation in the gut. Mice lacking Clostridium butyricum in the intestinal tract suffer from colitis. By contrast, butyric acid in the oral cavity worsens periodontal disease. Periodontal disease is a chronic condition in which periodontal tissue is exposed to virulence factors (such as butyric acid); however, no study has examined the effects of long-term exposure to butyric acid. The present study demonstrated that long-term exposure of human gingival fibroblasts (HGFs) to butyric acid induced cytostasis and apoptosis via the intrinsic and extrinsic pathways. Butyric acid inhibited the division of HGFs by altering expression of mRNAs encoding cyclins. Butyric acid induced apoptosis in HGFs via the intrinsic pathway, followed by activation of caspase 9; there was no DNA damage or p53 activation. Butyric acid also upregulated expression of TNF-α mRNA and protein by HGFs. Furthermore TNF-α induced apoptosis by activating caspase 8 (the extrinsic pathway) and by inducing production of pro-inflammatory cytokines. Taken together, the results show that butyric acid induced cytostasis and apoptosis in HGFs, accompanied by production of pro-inflammatory cytokines. It thus acts as a death ligand and plays a critical role as a prophlogistic substance.
Volume 482(4)
Pages 1122-1128
Published 2017-1-22
DOI 10.1016/j.bbrc.2016.11.168
PII S0006-291X(16)32042-3
PMID 27914813
MeSH Animals Apoptosis* Butyric Acid / chemistry* Caspase 8 / metabolism Cell Division Cell Survival Cytokines / metabolism DNA Damage Fibroblasts / drug effects Fibroblasts / metabolism* Gingiva / drug effects Gingiva / metabolism* Humans Inflammation Mice RAW 264.7 Cells Tumor Necrosis Factor-alpha / metabolism Tumor Suppressor Protein p53 / metabolism
IF 2.705
Times Cited 4
Resource
Human and Animal Cells RAW 264(RCB0535)