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

Objective: 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.

Conclusions: 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.