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. 2019 Nov 4:27:e20180713.
doi: 10.1590/1678-7757-2018-0713. eCollection 2019.

Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model

Hao Li  1 , Xinghua Zhong  1 , Wei Li  2 , Qi Wang  2
Affiliations

Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model

Hao Li et al. J Appl Oral Sci. .

Abstract

Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation.

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.

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Figures

Figure 1
Figure 1. Alveolar bone loss of the lingual side of mouse mandibular first and second molars was measured using scanning electron microscopy. Bone loss was represented by the area bordered by the green lines. Treatment with 1,25-dihydroxyvitamin D3 decreased the bone loss in periodontitis mice. Values are means ± SD (n=10). *P<0.05. N, normal control; P, Porphyromonas gingivalis infection; V, Porphyromonas gingivalis infection with 1,25-dihydroxyvitamin D3 treatment
Figure 2
Figure 2. Protein expression of VDR, AhR and CYP1A1 in the mouse gingival epithelium was examined using western blot analysis. Treatment with 1,25-dihydroxyvitamin D3 enhanced VDR expression and increased AhR and CYP1A1 production. Values are means ± SD (n=3). *P<0.05. N, normal control; P, Porphyromonas gingivalis infection; V, Porphyromonas gingivalis infection with 1,25-dihydroxyvitamin D3 treatment
Figure 3
Figure 3. Gingival epithelial VDR expression in each group, and AhR, CYP1A1, p-p65, NLRP3, ASC, caspase-1, IL-1β and IL-6 expression in normal control group was shown in immunohistochemical images. Treatment with 1,25-dihydroxyvitamin D3 enhanced VDR expression, while the VDR expression exhibited no significant difference between normal control and untreated periodontitis mice. N, normal control; P, Porphyromonas gingivalis infection; V, Porphyromonas gingivalis infection with 1,25-dihydroxyvitamin D3 treatment
Figure 4
Figure 4. Phosphorylation of NF-κB p65 and protein expression of NLRP3, ASC, caspase-1, IL-1β and IL-6 in the mouse gingival epithelium were examined using western blot analysis. Treatment with 1,25-dihydroxyvitamin D3 inhibited NF-κB p65 phosphorylation and decreased NLRP3, ASC, caspase-1, IL-1β and IL-6 expression. Values are means ± SD (n=3). *P<0.05. N, normal control; P, Porphyromonas gingivalis infection; V, Porphyromonas gingivalis infection with 1,25-dihydroxyvitamin D3 treatment
Figure 5
Figure 5. Protein expression of AhR, CYP1A1, p-p65, NLRP3, ASC, caspase-1, IL-1β and IL-6 in the mouse gingival epithelium was detected using immunohistochemical staining. After 1,25-dihydroxyvitamin D3 administration, the gingival epithelial expression of AhR and CYP1A1 was increased in mice with periodontitis, whereas the expression of p-p65, NLRP3, ASC, caspase-1, IL-1β and IL-6 was decreased. N, normal control; P, Porphyromonas gingivalis infection; V, Porphyromonas gingivalis infection with 1,25-dihydroxyvitamin D3 treatment
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