ABSTRACT
AIM: Previous data from our laboratory have demonstrated that localized aggressive periodontitis (LAP) patients produce elevated levels of pro-inflammatory cytokines in response to TLR4 and TLR2 ligation compared to unrelated and periodontally healthy controls (HC). The aim of the present work is to evaluate the contribution of TLR-related gene expression and miRNA regulation in LAP disease. MATERIAL AND METHODS: Peripheral blood mononuclear cells (PBMCs) from LAP and health control (HC) patients were isolated. Gene and miRNA expression involved in TLR signalling pathway and immunopathology were evaluated in unstimulated PBMCs by real-time PCR (RT-PCR). RESULTS: TICAM-1 (TRIF), FOS, IRAK1, TLR2 and CCL2 genes and the miRNAs miR-9-5p, miR-155-5p and 203a-3p, miR-147a, miR-182-5p and miR-183-5p were significantly up-regulated in LAP compared to HC. CONCLUSIONS: Most of the genes and miRNAs overexpressed here are directly or indirectly related to immune response and inflammation. This profile supports our previous findings that suggests LAP patients have a "hyper-responsive" phenotype upon activation of TLR pathway by periodontal pathogens.
Subject(s)
Aggressive Periodontitis , MicroRNAs , Aggressive Periodontitis/genetics , Gene Expression Profiling , Humans , Leukocytes, Mononuclear , MicroRNAs/genetics , Signal TransductionABSTRACT
OBJECTIVE: The purpose of this study was to investigate involvement of the P2X7 receptor in the rare condition, localized aggressive periodontitis. MATERIAL AND METHODS: Peripheral blood from 220 African Americans (103 with localized aggressive periodontitis and 117 healthy unrelated controls) was stimulated with lipopolysaccharide from E coli and Porphyromonas gingivalis. P2RX7 single nucleotide polymorphisms rs208294 (H155Y), rs1718119 (T348A), rs2230911 (T357S) and rs3751143 (E496A) were genotyped in 103 localized aggressive periodontitis patients and 117 healthy unrelated subjects. We examined genetic association between four P2RX7 single nucleotide polymorphisms and localized aggressive periodontitis, and tested for correlations between the single nucleotide polymorphisms and inflammatory response to lipopolysaccharide in blood samples from these patients. RESULTS: A significant association with localized aggressive periodontitis was observed with rs1718119 A (Thr) allele (P = 0.0063, odds ratio = 1.904) and with a haplotype containing this allele (P = 0.0075). Additionally, significant correlations with these data were found: the rs1718119 G allele correlated with greater production of IL-6, IL-2 and GM-CSF; the C (His) allele of rs208294 correlated with lower levels of IL-12p40; and the C (Thr) allele of rs2230911 correlated with greater levels of G-CSF. CONCLUSION: The data from these analyses support a possible biological relationship between P2RX7 genetic variants and inflammatory response in localized aggressive periodontitis patients.
Subject(s)
Aggressive Periodontitis/genetics , Polymorphism, Single Nucleotide , Receptors, Purinergic P2X7/genetics , Adolescent , Black or African American , Case-Control Studies , Child , Cytokines/analysis , Female , Genetic Association Studies , Haplotypes , Humans , Male , Young AdultABSTRACT
BACKGROUND: Previous studies have provided substantial evidence of the association of Aggregatibacter actinomycetemcomitans, and its highly leukotoxic JP2 genotype, with localized aggressive periodontitis (LAgP). The present study aims to evaluate presence of JP2 in individuals with LAgP after periodontal treatment. METHODS: Sixty African-American patients with LAgP, aged 5 to 25 years, were examined. At baseline, probing depth (PD), clinical attachment level (CAL), bleeding on probing, and plaque index were measured, and subgingival plaque was collected from LAgP diseased and healthy sites for each participant. Patients received whole-mouth ultrasonic debridement, scaling and root planing, and a 7-day prescription of amoxicillin and metronidazole. Participants were reevaluated and resampled and received regular maintenance therapy at 3, 6, and 12 months after treatment. Polymerase chain reaction was used to detect presence of the JP2 genotype before and after treatment. RESULTS: At baseline, the JP2 sequence was identified in 75% of LAgP diseased sites and in 56.67% of healthy sites. At 3, 6, and 12 months after treatment, the number of patients was 40, 31, and 31, respectively, and JP2 detection decreased to 17.5%, 6.45%, and 3.23%, respectively, in diseased sites (P <0.001) and to 2.5%, 3.23%, and 0%, respectively, in healthy sites (P <0.001). Clinical parameters of disease were also significantly reduced after therapy (P <0.001). Additionally, significant correlations were observed between JP2 presence and mean PD (P <0.002) and CAL (P <0.001), after therapy. CONCLUSION: Periodontal therapy was successful in reducing clinical parameters of LAgP and subgingival presence of JP2 in diseased and healthy sites.
