Stimulants of Toll-like receptors 2 and 4 are elevated in saliva of periodontitis patients compared with healthy subjects

• Published in: Journal of clinical periodontology Vol. 38; no. 4; pp. 318 - 325
• Main Authors: Lappin, D. F., Sherrabeh, S., Erridge, C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011; Blackwell
• Subjects: Adult; atherosclerosis; Atherosclerosis (general aspects, experimental research); Bacteriology; Bacteroides - immunology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Cells, Cultured; Chronic Periodontitis - immunology; Culture Media, Conditioned; endotoxin; Escherichia coli; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; HEK293 Cells; Humans; Insulin resistance; lipopeptide; Lipopeptides - analysis; Lipopolysaccharides - analysis; Lymphocyte Antigen 96 - analysis; Lysobacter - immunology; Male; Medical sciences; Non tumoral diseases; Otorhinolaryngology. Stomatology; periodontitis; Porphyromonas gingivalis - immunology; Prevotella - immunology; Prevotella intermedia - immunology; saliva; Saliva - chemistry; Salivary Proteins and Peptides - analysis; Stimulants; Toll-Like Receptor 2 - analysis; Toll-Like Receptor 4 - analysis; Toll-Like Receptor 5 - analysis; Toll-like receptors; Endocrinopathy; Human; Healthy subject; Stomatology; Metabolic diseases; Cardiovascular disease; Dentistry; Endotoxin; Vascular disease; Target tissue resistance; Toxin; Periodontal disease; Periodontitis; lipopeptide; Atherosclerosis; Toll-like receptors; Insulin resistance; Saliva; Biological receptor
• ISSN: 0303-6979; 1600-051X; 1600-051X
• DOI: 10.1111/j.1600-051X.2011.01702.x

Lappin DF, Sherrabeh S, Erridge C. Stimulants of Toll‐like receptors 2 and 4 are elevated in saliva of periodontitis patients compared with healthy subjects. J Clin Peridontol 2011; 38: 318–325. doi: 10.1111/j.1600‐051X.2011.01702.x Aim: Because the absorption of stimulants of Toll‐like receptor (TLR)2 and TLR4 from the gastrointestinal tract into the circulation has been proposed to promote the development of atherosclerosis and insulin resistance, we aimed to quantify the abundance of stimulants of TLR2 and TLR4 in human saliva. Methods: A recently developed bioassay based upon measurement of NF‐κB activation in TLR‐deficient human embryonic kidney (HEK)‐293 cells transfected with human TLR2 or TLR4 and calibrated with synthetic bacterial lipopeptide (Pam3CSK4) or Escherichia coli lipopolysaccharide (LPS), was used to establish the normal range of TLR stimulants in saliva of 20 healthy subjects and 20 subjects with periodontal disease. Results: Median soluble stimulants of TLR2 and TLR4 were significantly higher in saliva of periodontitis patients compared with saliva of healthy subjects; 3450 versus 77 ng/ml Pam3CSK4 equivalents (p<0.0001) and 138 versus 7 ng/ml LPS equivalents, respectively (p<0.0001). Salivary TLR stimulant levels remained relatively stable in healthy subjects over several days. Six strains of oral Gram‐negative bacteria, including Tannerella forsythensis, Lysobacter enzymogenes, Prevotella intermedia, Prevotella oris and Porphyromonas gingivalis, from a panel of nine examined did not stimulate TLR4‐dependent signalling. Conclusions: Elevated salivary TLR stimulants may represent a novel mechanism by which periodontitis increases the risk of developing cardiovascular disease and insulin resistance.