Female sex hormones modulate Porphyromonas gingivalis lipopolysaccharide-induced Toll-like receptor signaling in primary human monocytes.

BACKGROUND AND OBJECTIVE: Female sex hormones are elevated and are potential host response modifiers during pregnancy. Modulation of immune responses by estrogen and progesterone may be responsible for periodontal inflammation. Therefore, we aimed to investigate the role of ß-estradiol and progesterone in human monocyte immune responses, at cellular and molecular levels, to identify their role as a possible immunological link between pregnancy and periodontal disease. MATERIAL AND METHODS: Primary human monocytes were purified from human peripheral blood mononuclear cells by adherent method. Expression of Toll-like receptor (TLR) 2, 4 and CD14 was analyzed by flow cytometry. TLR2, TLR4, cyclooxygenase-2 (COX2), nuclear factor-kappa B (NF-κB) and NF-κB inhibitor-alpha mRNA expressions were measured using real-time reverse transcriptase-polymerase chain reaction and prostaglandin E2 secretion was assayed by enzyme-linked immunosorbent assay. NF-κB expression was also examined by immunofluorescence. Western blotting was performed to determine the activation of mitogen-activated protein kinase pathway. RESULTS: We report herein that both ß-estradiol and progesterone significantly reduced TLR2 expression at both protein and mRNA levels but had less of an effect on TLR4 expression in primary human monocytes. We also found that the hormones decreased monocyte cell surface protein expression of CD14. Significantly, ß-estradiol and progesterone dose-dependently downregulated monocyte expression of COX2 mRNA. Pretreatment monocytes with ß-estradiol or progesterone reduced effects of Porphyromonas gingivalis lipopolysaccharide (LPS) on COX2 mRNA expression and decreased prostaglandin E2 secretion by the monocytes. Furthermore, we demonstrated that both ß-estradiol and progesterone inhibited P. gingivalis LPS-induced NF-κB signaling pathway through the upregulation of NF-κB inhibitor-alpha expression. However, neither ß-estradiol nor progesterone altered the phosphorylation of the p38, the extracellular signal-regulated kinase 1/2 and the c-Jun N-terminal activated kinase in P. gingivalis LPS-stimulated monocytes. Thus, the inhibitory effects of these hormones on the response of human monocytes to P. gingivalis LPS appear to be independent on mitogen-activated protein kinase signaling pathway. CONCLUSION: The results of the present study suggest that ß-estradiol and progesterone could influence the immune response of human monocytes to periodontal pathogens and this process may have a role in the clinical manifestations of periodontal disease associated with pregnancy.

Do patients with aggressive periodontitis have evidence of diabetes? A pilot study.

BACKGROUND AND OBJECTIVE: Complex relationships exist between diabetes and periodontal disease. Diabetes is accepted as a risk factor for periodontal disease, and recent evidence supports the existence of a bidirectional relationship between these two diseases. It has been hypothesized that inflammation, lipids and adipokines may mediate these relationships. However, research regarding the above relationships with respect to aggressive periodontitis is very limited. This pilot study aimed to investigate whether patients with aggressive periodontitis (not previously diagnosed with diabetes) have evidence of diabetes and have altered serum levels of inflammatory mediators, lipids and adipokines. MATERIAL AND METHODS: Glycaemic control markers (random plasma glucose and glycated haemoglobin), inflammatory mediators (high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin-1ß, interleukin-6, interferon-γ and interleukin-18), lipids (triglycerides, total cholesterol and high-density lipoprotein-cholesterol) and adipokines (leptin, adiponectin and resistin) were measured in serum samples from 30 patients with aggressive periodontitis and 30 age- and sex-matched periodontally healthy control subjects, none of whom had a previous diagnosis of diabetes. RESULTS: Levels of glycaemic control markers, inflammatory mediators, lipids and adipokines were not significantly different (p > 0.05) between the aggressive periodontitis patients and healthy subjects for unadjusted and adjusted analyses (adjusting for body mass index, smoking, ethnicity, age and sex). The p-value for the adjusted analysis of adiponectin in female aggressive periodontitis patients compared with the female control subjects reached 0.064, the mean adiponectin level being lower in the female aggressive periodontitis patients (4.94 vs. 5.97 µg/mL). CONCLUSION: This pilot study provided no evidence to suggest that patients with aggressive periodontitis (not previously diagnosed with diabetes) have evidence of diabetes or altered serum levels of inflammatory mediators, lipids and adipokines.

Effects of IL-17 on human gingival fibroblasts.

Interleukin (IL)-17 is present in inflammatory periodontal lesions, thus suggesting a role in mediating inflammation. We tested the hypothesis that IL-17, especially when combined with interferon (IFN)-gamma, may modulate the responses of human gingival fibroblasts (HGFs). IL-17 induced IL-8 and minimal intercellular adhesion molecule (ICAM)-1 expression. It had no effect on expression of HLA-DR, CD40, or the immune-suppressive enzyme indoleamine 2,3-dioxygenase (IDO). The effects of IL-17 on HGFs were compared with those of IFN-gamma. Unlike IL-17, IFN-gamma augmented the expression of HLA-DR, ICAM-1, and IDO, but not IL-8. Thus, IL-17 and IFN-gamma induce different HGF responses when administered separately. Interestingly, when IL-17 and IFN-gamma were combined, marked enhancement of ICAM-1, IL-8, and IDO expression by HGFs was observed. These findings suggest that IL-17, especially when combined with IFN-gamma, could play an important role in immune modulation through stimulation of HGFs in periodontal disease.