Fisetin attenuates periodontitis through FGFR1/TLR4/NLRP3 inflammasome pathway.

Abstract

The purpose of the present study was to investigate the pharmacological effect of Fisetin on experimental periodontitis in rats and explore its potential mechanism. The ligature/LPS method was used to induce periodontitis in rats. LPS was employed to cause inflammation in Human gingival fibroblasts (HGF). The transfections with FGFR1 SiRNA, NLRP3 SiRNA and the selective TLR4 inhibitor TAK242 were used to investigate the mechanism of Fisetin-mediated inflammatory reaction in LPS-induced HGF. As a result, Fisetin reduced the alveolar bone gap, reversed histopathological lesion and inhibited serum inflammatory cytokine concentration in periodontitis rats. Fisetin decreased the inflammatory cytokine contents in the supernatant of LPS-induced HGF. The inhibitory effect of Fisetin might be attributed to FGFR1/TLR4/NLRP3 inflammasome pathway both in vivo and in vitro. The suppressions of FGFR1, TLR4 and NLRP3 proved that FGFR1/TLR4/NLRP3 signaling was involved in the Fisetin-mediated inflammatory response. Fisetin also inhibited NLRP3 priming. The data demonstrated that Fisetin attenuated periodontitis by inhibiting inflammatory reaction via FGFR1/TLR4/NLRP3 inflammasome pathway.

• Authors: Xin Huang, Hong Shen, Yiran Liu, Sainan Qiu, Yan Guo
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 95 Pg. 107505 (Jun 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 33725636 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Flavonols
• Inflammasomes
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Tlr4 protein, rat
• Toll-Like Receptor 4
• Fgfr1 protein, rat
• Receptor, Fibroblast Growth Factor, Type 1
• fisetin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cell Line
• Fibroblasts (drug effects)
• Flavonols (pharmacology, therapeutic use)
• Gingiva (cytology)
• Humans
• Inflammasomes (immunology)
• Lipopolysaccharides
• Male
• NLR Family, Pyrin Domain-Containing 3 Protein (immunology)
• Periodontitis (drug therapy, immunology)
• Rats, Sprague-Dawley
• Receptor, Fibroblast Growth Factor, Type 1 (immunology)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (immunology)
• Rats