Nuclear factor-kappaB p50 subunits in chronic periodontitis and Porphyromonas gingivalis lipopolysaccharide-pulsed dendritic cells.
The pathogenesis of a number of chronic inflammatory diseases has been linked to dysregulated functioning of nuclear transcription factor (NF)-kappaB. In the present study, we examine NF-kappaB activation in human oral mucosal tissues of chronic periodontitis (CP) patients. Electrophoretic mobility shift assay and DNA-binding enzyme-linked immunosorbent assays indicate elevated levels of transcriptionally repressive p50 subunits and an increased p50/p65 ratio in CP tissues compared to healthy controls. Because Porphyromonas gingivalis has been recognized to be a causal factor in CP, we used P. gingivalis lipopolysaccharide (LPS) for in vitro studies with monocyte-derived dendritic cells (MoDCs). Porphyromonas gingivalis LPS, unlike Escherichia coli LPS, induced an increased p50/p65 ratio in MoDCs. Using blocking antibodies, we demonstrated that while both Toll-like receptor 2 (TLR2) and TLR4 are required for MoDC maturation by P. gingivalis LPS, only TLR4 signaling is sufficient to induce cytokine secretion. Our results suggest that increased levels of transcriptionally repressive p50 may be characteristic of CP and might be a result of suboptimal NF-kappaB activation and dendritic cell maturation by P. gingivalis, a bacterium implicated in CP.
Jotwani
Ravi
R
Department of Periodontics and Implantology, Stony Brook University School of Dental Medicine, Stony Brook, NY, USA.
Moonga
Baljit S
BS
Gupta
Siddharth
S
Cutler
Christopher W
CW
D016866:Bacteroidaceae Infections / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D052002:NF-kappa B p50 Subunit / Q000276:immunology / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000737:chemistry; D011673:Pulsatile Flow / Q000187:drug effects / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha
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