Effects of 1,25-dihydroxyvitamin D3 on Experimental Periodontitis and AhR/NF-κB/NLRP3 Inflammasome Pathway in a Mouse Model

Overview

Journal J Appl Oral Sci

Specialty Dentistry

Date 2019 Nov 7

PMID 31691738

Citations 33

Authors

Hao Li

Xinghua Zhong

Wei Li

Qi Wang

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model.

Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining.

Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression.

Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.

Citing Articles

Exploring the Impact of Biological Agents on Protecting Against Experimental Periodontitis: A Systematic Review of Animal-Based Studies.

Oliveira G, Barbirato D, de Menezes B, Fuly M, Pelegrine H, Bonilha D Biomed Res Int. 2024; 2024:1716735.

PMID: 39654845 PMC: 11628168. DOI: 10.1155/bmri/1716735.

Prospective and challenges of locally applied repurposed pharmaceuticals for periodontal tissue regeneration.

El-Nablaway M, Rashed F, Taher E, Abdeen A, Taymour N, Soliman M Front Bioeng Biotechnol. 2024; 12:1400472.

PMID: 39605747 PMC: 11600316. DOI: 10.3389/fbioe.2024.1400472.

The role of aryl hydrocarbon receptor in the occurrence and development of periodontitis.

Wu L, Li X, Li J, Wang Y, Yang C, Zhao C Front Immunol. 2024; 15:1494570.

PMID: 39575260 PMC: 11580016. DOI: 10.3389/fimmu.2024.1494570.

Indigo alleviates psoriasis through the AhR/NF-κB signaling pathway: an and study.

Lin Y, Yang L, Wang D, Lei H, Zhang Y, Sun W PeerJ. 2024; 12:e18326.

PMID: 39465158 PMC: 11505883. DOI: 10.7717/peerj.18326.

Spermidine attenuates chondrocyte inflammation and cellular pyroptosis through the AhR/NF-κB axis and the NLRP3/caspase-1/GSDMD pathway.

Guo X, Feng X, Yang Y, Zhang H, Bai L Front Immunol. 2024; 15:1462777.

PMID: 39416781 PMC: 11479918. DOI: 10.3389/fimmu.2024.1462777.

References

Li J, Doty A, Glover S . Aryl hydrocarbon receptor signaling involves in the human intestinal ILC3/ILC1 conversion in the inflamed terminal ileum of Crohn's disease patients. Inflamm Cell Signal. 2017; 3(3). PMC: 5341615. DOI: 10.14800/ics.1404. View

Reins R, Mesmar F, Williams C, McDermott A . Vitamin D Induces Global Gene Transcription in Human Corneal Epithelial Cells: Implications for Corneal Inflammation. Invest Ophthalmol Vis Sci. 2016; 57(6):2689-98. PMC: 5995024. DOI: 10.1167/iovs.16-19237. View

Hayden M, Ghosh S . NF-κB in immunobiology. Cell Res. 2011; 21(2):223-44. PMC: 3193440. DOI: 10.1038/cr.2011.13. View

Hiyari S, Atti E, Camargo P, Eskin E, Lusis A, Tetradis S . Heritability of periodontal bone loss in mice. J Periodontal Res. 2015; 50(6):730-6. PMC: 4499504. DOI: 10.1111/jre.12258. View

Antonoglou G, Suominen A, Knuuttila M, Ylostalo P, Ojala M, Mannisto S . Associations between serum 25-hydroxyvitamin d and periodontal pocketing and gingival bleeding: results of a study in a non-smoking population in Finland. J Periodontol. 2015; 86(6):755-65. DOI: 10.1902/jop.2015.140262. View

Tipton D, Carter T, Dabbous M . Inhibition of interleukin 1β-stimulated interleukin-6 production by cranberry components in human gingival epithelial cells: effects on nuclear factor κB and activator protein 1 activation pathways. J Periodontal Res. 2013; 49(4):437-47. DOI: 10.1111/jre.12122. View

Vogel C, Khan E, Leung P, Gershwin M, Chang W, Wu D . Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-κB. J Biol Chem. 2013; 289(3):1866-75. PMC: 3894361. DOI: 10.1074/jbc.M113.505578. View

Arihiro S, Nakashima A, Matsuoka M, Suto S, Uchiyama K, Kato T . Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza and Upper Respiratory Infection in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis. 2019; 25(6):1088-1095. PMC: 6499936. DOI: 10.1093/ibd/izy346. View

Wang Q, Li H, Xie H, Fu M, Guo B, Ding Y . 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. J Steroid Biochem Mol Biol. 2013; 135:43-50. DOI: 10.1016/j.jsbmb.2013.01.008. View

10.

Dietrich T, Joshipura K, Dawson-Hughes B, Bischoff-Ferrari H . Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population. Am J Clin Nutr. 2004; 80(1):108-13. DOI: 10.1093/ajcn/80.1.108. View

11.

Manzella C, Singhal M, Alrefai W, Saksena S, Dudeja P, Gill R . Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR. Sci Rep. 2018; 8(1):6103. PMC: 5904159. DOI: 10.1038/s41598-018-24213-5. View

12.

Tada H, Matsuyama T, Nishioka T, Hagiwara M, Kiyoura Y, Shimauchi H . Porphyromonas gingivalis Gingipain-Dependently Enhances IL-33 Production in Human Gingival Epithelial Cells. PLoS One. 2016; 11(4):e0152794. PMC: 4825981. DOI: 10.1371/journal.pone.0152794. View

13.

Baelum V, Lopez R . Periodontal disease epidemiology - learned and unlearned?. Periodontol 2000. 2013; 62(1):37-58. DOI: 10.1111/j.1600-0757.2012.00449.x. View

14.

Ma Y, Wang Q, Yu K, Fan X, Xiao W, Cai Y . 6-Formylindolo(3,2-b)carbazole induced aryl hydrocarbon receptor activation prevents intestinal barrier dysfunction through regulation of claudin-2 expression. Chem Biol Interact. 2018; 288:83-90. DOI: 10.1016/j.cbi.2018.04.020. View

15.

Pludowski P, Holick M, Grant W, Konstantynowicz J, Mascarenhas M, Haq A . Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol. 2017; 175:125-135. DOI: 10.1016/j.jsbmb.2017.01.021. View

16.

Zhang A, Wang P, Ma X, Yin X, Li J, Wang H . Mechanisms that lead to the regulation of NLRP3 inflammasome expression and activation in human dental pulp fibroblasts. Mol Immunol. 2015; 66(2):253-62. DOI: 10.1016/j.molimm.2015.03.009. View

17.

Lu W, Song D, Yue J, Wang T, Zhou X, Zhang P . NLRP3 inflammasome may regulate inflammatory response of human periodontal ligament fibroblasts in an apoptosis-associated speck-like protein containing a CARD (ASC)-dependent manner. Int Endod J. 2016; 50(10):967-975. DOI: 10.1111/iej.12722. View

18.

Matsunawa M, Akagi D, Uno S, Endo-Umeda K, Yamada S, Ikeda K . Vitamin D receptor activation enhances benzo[a]pyrene metabolism via CYP1A1 expression in macrophages. Drug Metab Dispos. 2012; 40(11):2059-66. DOI: 10.1124/dmd.112.046839. View

19.

Du J, Li R, Yu F, Yang F, Wang J, Chen Q . Experimental study on 1,25(OH) D amelioration of oral lichen planus through regulating NF-κB signaling pathway. Oral Dis. 2017; 23(6):770-778. DOI: 10.1111/odi.12659. View

20.

Heaney R, Davies K, Chen T, Holick M, Barger-Lux M . Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2002; 77(1):204-10. DOI: 10.1093/ajcn/77.1.204. View