Association of <i>P2RX7</i> functional variants with localized aggressive periodontitis

Harris, Theodore H.; Wallace, Margaret R.; Huang, Huei-Jean; Li, Hua; Mohiuddeen, Azeem S.; Gong, Yan; Kompotiati, Theodora; Harrison, Peter; Aukhil, Ikramuddin; Shaddox, Luciana M.

doi:10.1111/jre.12682

Cited by 11 publications

(6 citation statements)

References 39 publications

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“…Thus, the decrease in GM-CSF levels seems beneficial in inflamed mucosa surfaces, including in periodontitis. Increased GM-CSF levels were associated with an allele of increased susceptibility to aggressive periodontitis ( Harris et al, 2020 ), whereas the destruction of the alveolar bone was dependent on GM-CSF in a mouse experimental model ( Lam et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Lactobacilli Attenuate the Effect of Aggregatibacter actinomycetemcomitans Infection in Gingival Epithelial Cells

et al. 2022

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Probiotics may be considered as an additional strategy to achieve a balanced microbiome in periodontitis. However, the mechanisms underlying the use of probiotics in the prevention or control of periodontitis are still not fully elucidated. This in vitro study aimed to evaluate the effect of two commercially available strains of lactobacilli on gingival epithelial cells (GECs) challenged by Aggregatibacter actinomycetemcomitans. OBA-9 GECs were infected with A. actinomycetemcomitans strain JP2 at an MOI of 1:100 and/or co-infected with Lactobacillus acidophilus La5 (La5) or Lacticaseibacillus rhamnosus Lr32 (Lr32) at an MOI of 1:10 for 2 and 24 h. The number of adherent/internalized bacteria to GECs was determined by qPCR. Production of inflammatory mediators (CXCL-8, IL-1β, GM-CSF, and IL-10) by GECs was determined by ELISA, and the expression of genes encoding cell receptors and involved in apoptosis was determined by RT-qPCR. Apoptosis was also analyzed by Annexin V staining. There was a slight loss in OBA-9 cell viability after infection with A. actinomycetemcomitans or the tested probiotics after 2 h, which was magnified after 24-h co-infection. Adherence of A. actinomycetemcomitans to GECs was 1.8 × 107 (± 1.2 × 106) cells/well in the mono-infection but reduced to 1.2 × 107 (± 1.5 × 106) in the co-infection with Lr32 and to 6 × 106 (± 1 × 106) in the co-infection with La5 (p < 0.05). GECs mono-infected with A. actinomycetemcomitans produced CXCL-8, GM-CSF, and IL-1β, and the co-infection with both probiotic strains altered this profile. While the co-infection of A. actinomycetemcomitans with La5 resulted in reduced levels of all mediators, the co-infection with Lr32 promoted reduced levels of CXCL-8 and GM-CSF but increased the production of IL-1β. The probiotics upregulated the expression of TLR2 and downregulated TLR4 in cells co-infected with A. actinomycetemcomitans. A. actinomycetemcomitans-induced the upregulation of NRLP3 was attenuated by La5 but increased by Lr32. Furthermore, the transcription of the anti-apoptotic gene BCL-2 was upregulated, whereas the pro-apoptotic BAX was downregulated in cells co-infected with A. actinomycetemcomitans and the probiotics. Infection with A. actinomycetemcomitans induced apoptosis in GECs, whereas the co-infection with lactobacilli attenuated the apoptotic phenotype. Both tested lactobacilli may interfere in A. actinomycetemcomitans colonization of the oral cavity by reducing its ability to interact with gingival epithelial cells and modulating cells response. However, L. acidophilus La5 properties suggest that this strain has a higher potential to control A. actinomycetemcomitans-associated periodontitis than L. rhamnosus Lr32.

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Section: Discussionmentioning

confidence: 99%

Lactobacilli Attenuate the Effect of Aggregatibacter actinomycetemcomitans Infection in Gingival Epithelial Cells

et al. 2022

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“…One SNP in LD (r 2 = 1.0, D’ = 1.0) is a gain-of-function variant, rs1718119 ( https://ldlink.nci.nih.gov/ ). rs1718119 is associated with higher pain intensity scores in females with diabetic peripheral neuropathy ( Ursu et al., 2014 ) and with inflammatory conditions including systemic lupus erythematosus, chronic obstructive pulmonary disease, and localised aggressive periodontitis ( Chen et al., 2013 ; Dai et al., 2018 ; Harris et al., 2020 ). Homozygous carriage of the minor allele of rs1718119 is associated with an ATP-induced increase of IL-1β from monocytes and with increased levels of IL-6 in whole blood ( Harris et al., 2020 ; Stokes et al., 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Neurocognitive outcomes in indonesians living with HIV are influenced by polymorphisms in the gene encoding purinergic P2X receptor 7

Gaff

Estiasari

Diafiri

et al. 2021

Brain, Behavior, & Immunity - Health

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The advent of effective antiretroviral therapy (ART) has decreased the prevalence and severity of HIV-associated neurocognitive disorders (HAND), but milder forms of HAND remain despite optimal treatment. Neuronal injury and loss due to inflammation may mediate HAND. P2X7R encodes purinergic P2X receptor 7 which influences neuroinflammatory pathways and carries polymorphisms associated with sensory neuropathy in HIV patients. We assessed associations between P2X7R polymorphisms and neurocognitive outcomes in Indonesian patients (n = 59) as they commenced ART and after 3, 6 and 12 months. Z-scores were calculated over 5 domains using local controls and evaluated as continuous variables. Optimal linear regression models identified polymorphisms influencing attention, memory, executive function, motor speed and total cognitive function at each time point. rs504677 was associated with lower executive and motor speed Z-scores at 0, 3, 6, and 12 months, and with memory at 0 and 12 months. Memory was positively influenced by carriage of the rs208296 minor allele at 0, 3 and 6 months and by carriage of the rs208307 minor allele at 0 and 12 months. Higher attention Z-scores associated with carriage of minor alleles of rs1653598 after 0 and 12 months. These also positively influenced executive function and motor speed after 0–6 months. This study identifies polymorphisms in P2X7R which influence domain-specific neurocognitive outcomes in HIV+ Indonesians prior to and shortly after commencing ART. This implicates purinergic P2X receptor 7 in the pathogenesis of HAND.

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“…However, patients often ignore the disease in its early stages. Therefore, most of them have already experienced symptoms including looseness, displacement or loss of teeth by the time they visit the clinic, which has had a severe impact on their daily behaviors including chewing and vocalization, and posing difficulties and challenges for clinical diagnosis and treatment (11,12). Localized aggressive periodontitis has a high incidence in clinical practice, usually caused by a mixed infection of many kinds of anaerobic bacteria (13).…”

Section: Discussionmentioning

confidence: 99%

Effects of xipayi mouth rinse combined with minocycline on localized aggressive periodontitis’ therapeutic effect and the levels of CRP, TNF-α, IL-6 in serum

Chen¹,

Wang²,

Zhifang³

et al. 2020

Ann Palliat Med

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Background: Localized aggressive periodontitis is rare periodontitis in clinical practice, which often occurs in young adults under 35 years old, seriously affecting patients' quality of life. As a tetracycline antibacterial drug, minocycline is also considered an essential choice to treat periodontal disease. However, few reports focused on the effect of xipayi mouth rinse combined with minocycline on periodontal pathogens. The goal of this study was to investigate the clinical effect of xipayi mouth rinse combined with minocycline in the treatment of localized aggressive periodontitis and its effect on the levels of CRP, TNF-α, and IL-6.Methods: Ninety-six patients with limited aggressive periodontitis were selected and randomly divided into two groups. Forty-eight patients in the control group were treated with xipayi mouth rinse after primary periodontal treatment. Then, 48 patients in the experimental group were treated with xipayi mouth rinse combined with minocycline after primary periodontal treatment. The periodontal probe was applied to detect periodontal plaque index (PLI), periodontal pocket depth (PD), sulcus bleeding index (SBI), gingival index (GL), and clinical attachment loss (CAL) before and after treatment in both groups of patients. ELISA was used for detecting the expression levels of CRP, TNF-α, and IL-6 in the serum of patients in two groups before and after treatment. We compared the recurrence rates of the two groups after a 1-year follow-up.Results: Compared with the control group, the PLI, PD, SBI, GL, CAL, and total masticatory efficiency of the experimental group were significantly better than those of the control group. The levels of inflammatory factors CRP, TNF-α, and IL-6 were significantly declined, and the total effective rate of treatment was significantly elevated. After follow-up, it was found there was no noticeable difference in the recurrence rate between the two groups.Conclusions: Xipayi mouth rinse, combined with minocycline in the treatment of localized aggressive periodontitis, can significantly improve the periodontal gingival condition and reduce the level of inflammatory factors. Also, the efficacy of the treatment was significant. This experiment has provided ideas for improving the clinical treatment of patients with localized aggressive periodontitis.

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Association of P2RX7 functional variants with localized aggressive periodontitis

Cited by 11 publications

References 39 publications

Lactobacilli Attenuate the Effect of Aggregatibacter actinomycetemcomitans Infection in Gingival Epithelial Cells

Lactobacilli Attenuate the Effect of Aggregatibacter actinomycetemcomitans Infection in Gingival Epithelial Cells

Neurocognitive outcomes in indonesians living with HIV are influenced by polymorphisms in the gene encoding purinergic P2X receptor 7

Effects of xipayi mouth rinse combined with minocycline on localized aggressive periodontitis’ therapeutic effect and the levels of CRP, TNF-α, IL-6 in serum

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