Alendronate regulates cytokine production induced by lipid A through nuclear factor-κB and Smad3 activation in human gingival fibroblasts

2011 ◽  
Vol 46 (1) ◽  
pp. 13-20 ◽  
Author(s):  
R. Tamai ◽  
A. Sugiyama ◽  
Y. Kiyoura
Keyword(s):  
Lipid A ◽  
Cytokine Production ◽  
Nuclear Factor Κb ◽  
Human Gingival Fibroblasts ◽  
Nuclear Factor ◽  
Gingival Fibroblasts

scholarly journals Biological Activities of Bacteroides forsythus Lipoproteins and Their Possible Pathological Roles in Periodontal Disease

2004 ◽  
Vol 72 (3) ◽  
pp. 1318-1325 ◽  
Author(s):  
Akira Hasebe ◽  
Atsutoshi Yoshimura ◽  
Takeshi Into ◽  
Hideo Kataoka ◽  
Saori Tanaka ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Cell Line ◽  
Biological Activities ◽  
Leukemia Cell ◽  
Nuclear Factor Κb ◽  
Human Gingival Fibroblasts ◽  
Leukemia Cell Line ◽  
Nuclear Factor ◽  
Gingival Fibroblasts ◽  
Toll Like Receptor

ABSTRACT Bacteroides forsythus is a gram-negative, anaerobic, fusiform bacterium and is considered to be an etiological agent in periodontal disease. A lipoprotein fraction prepared from B. forsythus cells by Triton X-114 phase separation (BfLP) activated human gingival fibroblasts and a human monocytic cell line, THP-1, to induce interleukin-6 production and tumor necrosis factor alpha production. BfLP was found to be capable of inducing nuclear factor-κB translocation in human gingival fibroblasts and THP-1 cells. By using Chinese hamster ovary K1 cells transfected with Toll-like receptor genes together with a nuclear factor-κB-dependent CD25 reporter plasmid, it was found that signaling by BfLP was mediated by Toll-like receptor 2 but not by CD14 or Toll-like receptor 4. BfLP induced apoptotic cell death in human gingival fibroblasts, KB cells (an oral epithelial cell line), HL-60 cells (a human myeloid leukemia cell line), and THP-1 cells but not in MOLT4 cells (a T-cell leukemia cell line). Caspase-8, an initiator caspase in apoptosis, was found to be activated in these cells in response to BfLP stimulation. Thus, this study suggested that BfLP plays some etiological roles in oral infections, especially periodontal disease, by induction of cell activation or apoptosis.

Amphotericin B Up-regulates Lipid A-induced IL-6 Production via Caspase-8

2012 ◽  
Vol 91 (7) ◽  
pp. 709-714 ◽  
Author(s):  
R. Tamai ◽  
M. Sugamata ◽  
Y. Kiyoura
Keyword(s):  
Amphotericin B ◽  
Inflammatory Cytokine ◽  
Lipid A ◽  
Cytokine Production ◽  
Cultured Cells ◽  
Human Gingival Fibroblasts ◽  
Caspase 8 ◽  
Gingival Fibroblasts ◽  
Inflammatory Cytokine Production ◽  
Pre Treatment

Amphotericin B, an antifungal drug used to treat candidiasis, has been reported to induce pro-inflammatory cytokine production in cultured cells. This study investigated the effects of amphotericin B on pro-inflammatory cytokine production in response to lipid A, the bioactive component of lipopolysaccharide (LPS) in the cell walls of Gram-negative bacteria. Amphotericin B alone elicited a slight increase in interleukin (IL)-6 and IL-8 production by human gingival fibroblasts. However, amphotericin B synergistically up-regulated lipid A-induced production of IL-6 and IL-8. While amphotericin B minimally activated nuclear factor (NF)-κB, it synergistically increased lipid A–induced NF-κB activation. Pre-treatment with methyl-β-cyclodextrin (MβCD), a cholesterol-binding agent, reduced IL-6 and IL-8 production in human gingival fibroblasts. Cholesterol-saturated MβCD also reversed cytokine production, suggesting that the synergistic production of cytokines by amphotericin B and lipid A is dependent on cholesterol-rich microdomains. Amphotericin B activated caspase-8. In addition, a caspase-8 inhibitor inhibited IL-6 production by amphotericin B and lipid A. This suggests that caspase-8 is required for the synergistic production of IL-6 by amphotericin B and lipid A. Collectively, our results suggest that periodontal treatment carried out before amphotericin B treatment may protect against lipid A-induced pro-inflammatory cytokine production.

scholarly journals Fusobacterium nucleatum Facilitates Apoptosis, ROS Generation, and Inflammatory Cytokine Production by Activating AKT/MAPK and NF-κB Signaling Pathways in Human Gingival Fibroblasts

2019 ◽  
Vol 2019 ◽  
pp. 1-22 ◽  
Author(s):  
Wenyan Kang ◽  
Zhilong Jia ◽  
Di Tang ◽  
Zhanwei Zhang ◽  
Hui Gao ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Fusobacterium Nucleatum ◽  
Human Gingival Fibroblasts ◽  
Ros Generation ◽  
Gingival Fibroblasts ◽  
Inflammatory Cytokine Production ◽  
Pathogenic Effects

Fusobacterium nucleatum (F. nucleatum) plays key roles in the initiation and progression of periodontitis. However, the pathogenic effect of F. nucleatum on human oral tissues and cells has not been fully evaluated. In this study, we aimed to analyze the pathogenic effects of F. nucleatum on human gingival fibroblasts (GFs) and clarify the potential mechanisms. RNA-sequencing analysis confirmed that F. nucleatum significantly altered the gene expression of GF as the stimulation time increased. Cell counting and EdU-labeling assays indicated that F. nucleatum inhibited GF proliferation and promoted cell apoptosis in a time- and dose-dependent manner. In addition, cell apoptosis, intracellular reactive oxygen species (ROS) generation, and proinflammatory cytokine production were dramatically elevated after F. nucleatum stimulation. Furthermore, we found that the AKT/MAPK and NF-κB signaling pathways were significantly activated by F. nucleatum infection and that a large number of genes related to cellular proliferation, apoptosis, ROS, and inflammatory cytokine production downstream of AKT/MAPK and NF-κB signaling pathways were significantly altered in F. nucleatum-stimulated GFs. These findings suggest that F. nucleatum inhibits GF proliferation and promotes cell apoptosis, ROS generation, and inflammatory cytokine production partly by activating the AKT/MAPK and NF-κB signaling pathways. Our study opens a new window for understanding the pathogenic effects of periodontal pathogens on the host oral system.

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