Influence of genetic regulatory effects modified by environmental immune activation on periapical disease.

The objective of this study was to compare the periradicular responses in endodontic infections among members of two populations: an urban Brazilian population and a non-mixed indigenous population. Samples were collected immediately and 7 days after the cleaning and shaping procedures (after reducing the intracanal microbial load) in an attempt to characterize the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-9, interferon (IFN)-γ, IL-17, IL-10, and the chemokines CXCR4, CCL2/monocyte chemotactic protein (MCP)-1, and CCR6. The endogenous cytokine and chemokine expression levels were analyzed using real-time PCR. Only the urban population showed a significant increase in TNF-α, CCL2/MCP-1, CXCR4, and CCR6 expression following the cleaning and shaping of the root canal system. The IFN-γ levels were increased at the 2nd collection (p < 0.05) in the indigenous population. In turn, a significant increase in IL-10 and IL-17 expression (p < 0.05) was observed after the cleaning and shaping procedures (2nd collection) in both populations. No significant differences in the IL-1ß, IL-9, and CCL4 expression levels were observed between the 1st and 2nd collections in both populations. The results demonstrate a cytokine and chemokine expression profile that is specific to each analyzed population. However, immune modulation mediated by IL-10 began on the 7th day after the beginning of the endodontic treatment in both populations.

Immunological profile of periapical endodontic infections from HIV- and HIV+ patients.

AIM: To evaluate CD4(+) CD28(+) and CD8(+) T-cell genes and the gene expression of IFN-γ, TNF-α, IL-1-ß, IL-17A, IL-10, CCL-2/MCP-1, CCL-4, CCL-5 (RANTES), CXCR4, CCR5 and RANKL from cells in the periapical interstitial fluid from root canal infections in healthy patients (HIV-) and HIV-positive individuals (HIV+). METHODOLOGY: Subjects included 20 HIV- and 23 HIV+ patients referred to the School of Dentistry at the Universidade Federal de Minas Gerais (Belo Horizonte, MG, Brazil). Almost all HIV+ patients were undergoing highly active antiretroviral therapy (HAART). Clinical samples were taken from teeth with pulp necrosis, and no patients had acute periapical symptoms at the time of the appointments. After cleaning and drying, 3 paper points were introduced into the root canal, passing passively through the root apex (2 mm) into the periapical tissues for 1 min. The samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize those gene expressions using real-time PCR. RESULTS: Significantly higher levels of CD4(+) CD28(+) and CD8(+) T cells in teeth with restrained bacterial loads (second collection) compared with the first collection were observed in both HIV- and HIV+ samples. In HIV- patients, an increase in IL-10 and CXCR4 expression was demonstrated as well as a decrease in pro-inflammatory cytokines such as RANKL, IFN-γ, IL1-ß and CCL5. However, in HIV+ patients an increase in cytokines IFN-γ, IL-1-ß, TNF-α and IL-17A, and chemokines CCL-2, CXCR4 and CCR5 were observed. The chemokine CCL-5 was not detected in HIV+ individuals. CONCLUSIONS: These findings suggest that after reducing the root canal bacterial load in HIV- individuals an anti-inflammatory response is generated whilst in HIV+ patients a pro-inflammatory response is sustained in the periapical area.

Genetic susceptibility to periapical disease: conditional contribution of MMP2 and MMP3 genes to the development of periapical lesions and healing response.

INTRODUCTION: It has been proposed that individual genetic predisposition may contribute to a persistent apical periodontitis condition. Matrix metalloproteinases (MMPs) are associated with levels of inflammation and are involved in caries, pulpal, and periapical tissue destruction. MMPs also play a major role in bone resorption. In this study, we hypothesized that polymorphisms in MMP genes and their regulators may contribute to an individual's increased susceptibility to apical tissue destruction in response to deep carious lesions. METHODS: Sixteen hundred radiographic records obtained through the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository were screened for subjects with deep carious lesions in dentin with or without periapical lesions (≥ 3 mm). DNA samples of 268 patients were sorted into 2 groups: 158 cases with deep carious lesions but no periapical lesions (controls) and 110 cases with periapical lesions and deep carious lesions (cases). Sixteen SNP markers in MMP2, MMP3, MMP9, MMP13, MMP14, and TIMP2, were selected for genotyping. Genotypes were generated by endpoint analysis in a real-time polymerase chain reaction instrument. Analyses were performed comparing cases and controls. Allele and genotypic frequencies and haplotype analysis were calculated using the PLINK program. RESULTS: An association was found for MMP3 rs639752 (P = .03) and rs679620 (P = .004) genotypes in individuals with periapical lesions. We also observed altered transmission of MMP2 marker haplotypes (P = .000004) in these individuals. CONCLUSIONS: Variations in MMP2 and MMP3 are associated with periapical lesion formation in individuals with untreated deep carious lesions. Future studies could help predict host susceptibility to developing periapical lesions.