2. Academic Validation
  3. Beyond transcription, aryl hydrocarbon receptor plays a protective role in periodontitis by interacting with CaMKII

Beyond transcription, aryl hydrocarbon receptor plays a protective role in periodontitis by interacting with CaMKII

  • J Periodontol. 2024 Jul 5. doi: 10.1002/JPER.24-0021.
Xuwen Zeng 1 2 3,  Meiting Feng 1,  Jiawei Lu 1,  Ruiling Wang 1,  Li Deng 1,  Yanan Yang 1,  Lijun Luo 1
Affiliations

Affiliations

  • 1 Department of Periodontology, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
  • 2 i3S - Instituto de Investigação e Inovação em Saúde (Institute for Research and Innovation in Health), University of Porto, Porto, Portugal.
  • 3 IBMC - Instituto de Biologia Molecular e Celular (Institute for Molecular and Cell Biology), University of Porto, Porto, Portugal.
PMID: 38967396 DOI: 10.1002/JPER.24-0021
Abstract

Background: The Aryl Hydrocarbon Receptor (AhR) has been studied as an intracellular pattern recognition receptor that can identify Bacterial pigments. To identify a potential therapeutic target for periodontitis, we investigated the expression of AhR in periodontitis and its role in the pathogenesis of periodontitis.

Methods: First, we analyzed AhR expression in a single-cell dataset from human periodontal tissue. Quantitative polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry were used to verify the AhR level. Later, we determined the phenotypes of ligature-induced periodontitis in myeloid-specific AhR-deficient mice (Lyz2-Cre+/- AhRfx/fx), after which RNA Sequencing (RNA-seq), qPCR, Western blot, immunofluorescence, and immunohistochemistry were used to investigate the impacts of AhR on periodontitis and its mechanism. Finally, we determined the therapeutic effect of AhR agonist 6-Formylindolo[3,2-b]carbazole (FICZ) administration on murine periodontitis and verified the effects of FICZ on macrophage polarization in vitro.

Results: AhR expression was enhanced in macrophages from periodontitis patients. Deletion of AhR from macrophages aggravated ligature-induced periodontitis and promoted the inflammatory response. Calcium/calmodulin-stimulated protein kinase II (CaMKII) phosphorylation was accelerated in AhR-deficient macrophages. Inhibiting CaMKII phosphorylation ameliorated periodontitis in Lyz2-Cre+/- AhRfx/fx mice. FICZ treatment blocked alveolar bone loss and relieved periodontal inflammation. FICZ diminished M1 macrophage polarization and promoted M2 macrophage polarization upon M1 macrophage induction.

Conclusion: AhR played a protective role in the pathogenesis of periodontitis by orchestrating macrophage polarization via interacting with the CaMKII signaling pathway.

Keywords

CaMKII; aryl hydrocarbon receptor; macrophage; pattern recognition receptor; periodontitis.

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