Mechanisms Underlying Enterococcus faecalis-Induced Tumor Necrosis Factor-alpha Production in Macrophages.
- Author:
Eun Kyoung CHOI
1
;
Dae Eob KIM
;
Won Mann OH
;
Yun Woong PAEK
;
In Chol KANG
Author Information
1. Department of Oral Microbiology, Dental Science Research Institute, Chonnam National University Dental School, Gwangju 500-757, Korea. ickang@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
Enterococcus faecalis;
tumor necrosis factor-alpha;
macrophage
- MeSH:
Bacteria;
Cell Line;
Cytochalasin D;
Cytokines;
Endocytosis;
Enterococcus;
Enterococcus faecalis;
Gene Expression;
Macrophages;
NF-kappa B;
p38 Mitogen-Activated Protein Kinases;
Periapical Periodontitis;
Phosphotransferases;
Reactive Oxygen Species;
RNA, Messenger;
Transcription Factor AP-1;
Tumor Necrosis Factor-alpha;
Up-Regulation
- From:International Journal of Oral Biology
2010;35(2):43-49
- CountryRepublic of Korea
- Language:English
-
Abstract:
Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-alpha. The present study investigated the mechanisms involved in TNF-alpha production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-alpha. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-alpha by E. faecalis. In addition, antioxidant treatment reduced TNF-alpha production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-alpha expression by RAW 264.7 cells. Furthermore, activation of NF-kappaB and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-alpha in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-kappaB, and AP-1.
