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

Abstract

Effects of 1,25-dihydroxyvitamin D 3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model 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 D 3 (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.

Vitamin D3 ameliorates nitrogen mustard‐induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3–SOD2–mtROS signaling pathway

“…Moreover, VD3 reduces oxidative stress‐mediated inflammation predominantly induced by particulate matter through inactivating the NLRP3 inflammasome 18 . VD3 has additionally been shown to attenuate periodontitis via inactivating NLRP3 inflammasome in the mouse model 19 . These published data suggest the involvement of the NLRP3 inflammasome in the protective effects of VD3.…”

Vitamin D and Periodontitis: A Systematic Review and Meta-Analysis

“…Others supported the idea that patients with higher levels of vitamin D were related to less bleeding on probing (BoP) comparing to patients with lower levels [ 34 ]. In addition, in vitro studies demonstrated that vitamin D may decrease the number of Porphyromonas gingivalis through active autophagy [ 37 ] and might decrease the inflammatory burden of periodontitis in rodent models [ 38 , 39 , 40 , 41 ]. Furthermore, the association between vitamin D levels and periodontitis has been systematically investigated [ 42 , 43 , 44 , 45 ]; however, none of these studies were able to produce quantitative synthesis.…”

<p>Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway</p>

“…12 The expression of NLRP3 inflammasomes is upregulated in periodontitis, 13 and the inhibition of the NLRP3 inflammasome can reduce the periodontitis in mice. 14 Thus, inhibition of NLRP3 inflammasome activation and the resulting pyroptosis may be essential in improving periodontitis.…”