Porphyromonas gingivalis infection promotes inflammation via inhibition of the AhR signalling pathway in periodontitis.

Abstract

Porphyromonas gingivalis (P. gingivalis) is a key pathogen of chronic periodontitis. Aryl hydrocarbon receptor (AhR) is essential in immune homeostasis via modulation of pro-inflammatory cytokines production and indoleamine 2,3-dioxygenase (IDO). In this study, it is demonstrated that P. gingivalis may regulate AhR signalling in periodontitis, which provides a potential target for further immune regulation studies in periodontitis. Experimental periodontitis was induced in C57BL/6 mice by silk ligature and P. gingivalis oral inoculation. The alveolar bone resorption was examined using Micro-CT. Histological structures were observed and related cytokines involved in AhR signalling pathway were analysed. RAW264.7 cells were pretreated with AhR agonist (FICZ) and antagonist (CH223191) and infected with P. gingivalis subsequently. The levels of IDO, AhR and other related cytokines were measured. To demonstrate IDO activity, the concentrations of tryptophan (Trp) and kynurenine (Kyn) were assessed by HPLC. Histological analysis of periodontitis mice showed distinct alveolar bone resorption and inflammatory cell infiltration. The level of AhR and its downstream target factors were significantly decreased in inflamed gingival tissue. Furthermore, RAW 264.7 cells incubated by P. gingivalis exhibited increased pro-inflammatory cytokines production and decreased AhR, CYP1A1, CYP1B1, and IDO expression. Decreased IDO activity was observed as decreased Kyn/Trp ratio in the supernatant. Moreover, FICZ decreased the pro-inflammatory cytokines levels in P. gingivalis infected cells. It is concluded that P. gingivalis may promote inflammatory responses via inhibiting the AhR signalling pathway in periodontitis.

• Authors: Ting Hao, Rui Zhang, Tian Zhao, Juan Wu, Wai Keung Leung, Jie Yang, Weibin Sun
• Journal: Cell proliferation (Cell Prolif) Vol. 56 Issue 2 Pg. e13364 (Feb 2023) ISSN: 1365-2184 [Electronic] England
• PMID: 36446468 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

Chemical References

• Receptors, Aryl Hydrocarbon
• Cytokines

Topics

• Animals
• Mice
• Porphyromonas gingivalis (metabolism)
• Receptors, Aryl Hydrocarbon
• Mice, Inbred C57BL
• Periodontitis (pathology)
• Inflammation
• Cytokines (metabolism)
• Alveolar Bone Loss (pathology)