Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic complications. Periodontitis is an inflammatory disease that is characterized by increased oxidative stress, and the risk for periodontitis is increased significantly in diabetic subjects. In this study, we examined the superoxide (O 2 − )-generating reduced nicotinamide adenine dinucleotide phosphate-oxidase complex and protein kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped according to glycemic control and the severity of periodontitis. Neutrophils from diabetic patients with moderate [amount of glycated hemoglobin (HbA 1c ) between 7.0% and 8.0%] or poor (HbA 1c >8.0%) glycemic control released significantly more O 2 − than neutrophils from diabetic patients with good glycemic control (HbA 1c <7.0%) and neutrophils from nondiabetic, healthy individuals upon stimulation with 4β-phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. Depending on glycemic status, neutrophils from these patients also exhibited increased activity of the soluble-and membrane-bound forms of PKC, elevated amounts of diglyceride, and enhanced phosphorylation of p47-phox during cell stimulation. In addition, we report a significant correlation between glycemic control (HbA 1c levels) and the severity of periodontitis in diabetic patients, suggesting that enhanced oxidative stress and increased inflammation exacerbate both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil priming, where elevated PKC activity results in increased phosphorylation of p47-phox and O 2 − release.

These data confirm the high prevalence and severity of periodontitis in the diabetic population, and support the association between poor glycemic control and periodontal disease. The low prevalence of some of the IL-1 gene polymorphisms in the ethnic groups included in this study limits the validity of conclusions on genotype associations with clinical findings, but there was a trend suggesting that allele 1 at IL-1B (-511) and IL-1B (+3954) was overrepresented among diabetics with periodontal disease.

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Background Polymorphonuclear leukocyte (PMN) is the predominant innate immune cell type activated in acute inflammation. The aim of this study was to determine the impact of Enamel matrix derivative (EMD) on superoxide (O2−) generation, chemotaxis, and matrix metalloproteinase 8 (MMP 8) secretion by PMN in vitro to better understand the role of EMD in surgical wound healing. Methods PMN were isolated from healthy volunteers (N = 14). Superoxide generation was measured using a cytochrome-C reduction assay. Chemotaxis was measured in a modified Boyden chamber. MMP 8 secretion was analyzed by Western blotting. A relative density method was used to determine the percent of MMP 8 released from the PMN in relation to the total cellular MMP 8 content. Results O2− generation was significantly elevated when PMN were stimulated with EMD (200 μg/ml) (P<0.01). Secondary stimulation of PMN with 1 μM fMLP trigged earlier and more sustained O2− generation with EMD. EMD significantly increased PMN chemotactic activity (P<0.05). Combined stimulation with EMD plus formyl-methionyl-leucyl-phenylalanine (fMLP) resulted in significantly higher chemotaxis compared to fMLP alone (P<0.05). Conversely, EMD did not induce MMP 8 secretion from PMN. MMP 8 secretion by PMN in response to fMLP or serum-opsonized zymosan (OZ) stimulation was significantly inhibited by EMD (P<0.05). Conclusion EMD has specific, differential actions on PMN that suggest potential for enhancement of wound healing; bacterial and tissue debris clearance (O2− generation and chemotaxis) and suppress tissue damage and degradation (MMP 8). Taken together, the data suggest that EMD enhances wound healing and reduces inflammation.

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