Impact of p. Gingivalis-induced chronic apical periodontitis on systemic iron homeostasis via the hepatic IL-6/STAT3/Hepcidin signaling pathway.

BACKGROUND AND AIMS

Chronic apical periodontitis (CAP), an inflammatory disease of the oral cavity caused by bacterial infections with Porphyromonas gingivalis (P. gingivalis) as a key pathogen, has been associated with systemic effects, potentially influencing distant organs including liver. The liver plays a key role in iron metabolism and immunity by hepcidin. This study aims to investigate the impact of P. gingivalis-induced CAP on liver and systemic iron metabolism, focusing on the role of the IL-6/STAT3 signaling pathway in hepatic hepcidin synthesis.

METHODS

A murine model of CAP was established by pulp chamber infection with P. gingivalis. Serum levels of IL-6, ferritin, and hepcidin were measured via ELISA. High-throughput sequencing was used to analyze hepatic gene expression, and immunohistochemistry with fluorescent staining was performed to validate protein expression in liver tissues.

RESULTS

CAP led to significant changes in serum iron, ferritin, and IL-6. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed enrichment in pathways like JAK/STAT signaling and acute-phase responses, and gene set enrichment analysis (GSEA) also indicated activation of IL-6/JAK/STAT3 signaling pathway. Iimmunofluorescence confirmed increased IL-6, p-STAT3, and hepcidin expression. These levels were alleviated by stattic treatment, mitigating CAP-induced inflammatory and iron-regulatory effects.

CONCLUSION

P. gingivalis-induced CAP triggered systemic inflammation and disrupts iron metabolism via the IL-6/STAT3 signaling pathway, potentially affecting liver function. Targeting this pathway may offer therapeutic strategies for managing iron dysregulation in chronic inflammatory diseases like CAP.