Proinflammatory gene expression at chronic periodontitis and peri-implantitis sites in patients with or without type 2 diabetes.
BACKGROUND
Diabetes and periodontal diseases are often associated. Both have highly inflammatory components, but the role played by distinct phlogistic mediators in their pathogenesis is not fully understood and remains controversial. The purpose of this study is to evaluate whether type 2 diabetes alters the expression of inflammatory mediators in sites with chronic periodontitis (CP) or peri-implantitis (P-IM).


METHODS
The expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and -8, and monocyte chemotactic protein (MCP)-1 plus key CC chemokine receptors (CCR1 through 5) and CXC chemokine receptors (CXCR1 through 3) was quantified by real-time polymerase chain reaction (PCR) in gingival or peri-implant biopsies from 135 patients with well-controlled or poorly controlled diabetes and periodontal disease, 65 patients with periodontal disease but otherwise healthy, and 90 systematically and periodontally healthy subjects. Western blots were performed.


RESULTS
Relative to controls, in patients without diabetes and patients with well-controlled diabetes, TNF-alpha, CCR5, and CXCR3 expression was exclusively higher in sites with P-IM (P <0.01), whereas IL-6 and -8 were overexpressed in sites with CP and, even more, in sites with P-IM (P <0.01). In patients with poor glycemic control, TNF-alpha, CCR5, and CXCR3 mRNAs were increased in sites with CP (P <0.01). A statistically significant higher IL-6 and -8 expression from patients without diabetes and patients with well-controlled diabetes was observed compared to patients with poorly controlled diabetes. Regardless of metabolic/glycemic status, MCP-1 and CCR2 and 4 were markedly higher in both of the oral pathologies examined (P <0.01). At the protein levels, Western blot experiments confirmed the real-time PCR results.


CONCLUSIONS
These findings showed that: 1) in subjects without diabetes and patients with well-controlled diabetes, TNF-alpha, CCR5, and CXCR3 may constitute distinctive biomarkers of P-IM; 2) poor glycemic control abolished the differences between CP and P-IM regarding the expression of these mediators; and 3) type 2 diabetes affected the expression of TNF-alpha, IL-6 and -8, CCR5, and CXCR3.
Venza
Isabella
I
Department of Surgical Specialities, University of Messina, 98125 Messina, Italy.
Visalli
Maria
M
Cucinotta
Maria
M
De Grazia
Giuseppina
G
Teti
Diana
D
Venza
Mario
M
D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000209:etiology / Q000276:immunology*; D015921:Dental Implants / Q000009:adverse effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000032:analysis; D054388:Receptors, CCR / Q000235:genetics / Q000378:metabolism*; D054387:Receptors, CXCR / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D015921:Dental Implants; D018836:Inflammation Mediators; D007378:Interleukins; D054388:Receptors, CCR; D054387:Receptors, CXCR; D014409:Tumor Necrosis Factor-alpha; D012313:RNA