Porphyromonas gingivalis ‐Lipopolysaccharide Induced Gingival Fibroblasts Trained Immunity Sustains Inflammation in Periodontitis

作者：J. Liu, Haoyang Tian, Ji-Min Ju, Fujiao Nie, Qiuyue Yin, Jingjing Zhao, Suli Wang, Hongmei Guo, Pishan Yang · 发表于：Journal of Periodontal Research · 年份：2024 · DOI：10.1111/jre.13372 · 被引用次数：16 · 研究领域：Immune responses and vaccinations、Oral microbiology and periodontitis research、Gut microbiota and health

AIM: To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis. METHODS: Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in vitro model, with relevant markers assessed via enzyme-linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs. RESULTS: Compared with untrained cells, GFs trained with Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) exhibited a significant increase in IL-6 and TNF-α secretion, enhanced glycolytic metabolism, and enriched mono-methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF-α and IL-6. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to P. gingivalis-LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs. CONCLUSION: This study novelly discovered that both P. gingivalis-LPS-stimulated HGFs and IGFs in peri...