Porphyromonas gingivalis Outer Membrane Vesicles Stimulate Gingival Epithelial Cells to Induce Pro-Inflammatory Cytokines via the MAPK and STING Pathways.
Yuta UemuraYuka HiroshimaAyano TadaKeiji MurakamiKaya YoshidaYuji InagakiTomomi KuwaharaAkikazu MurakamiHideki FujiiHiromichi YumotoPublished in: Biomedicines (2022)
Porphyromonas gingivalis ( Pg ) is a keystone pathogen associated with chronic periodontitis and produces outer membrane vesicles (OMVs) that contain lipopolysaccharide (LPS), gingipains, and pathogen-derived DNA and RNA. Pg -OMVs are involved in the pathogenesis of periodontitis. Pg -OMV-activated pathways that induce the production of the pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in the human gingival epithelial cell line, OBA-9, were investigated. The role of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in levels of Pg -OMV-induced pro-inflammatory cytokines was investigated using Western blot analysis and specific pathway inhibitors. Pg -OMVs induced IL-6 and IL-8 production via the extracellular signal-regulated kinase (Erk) 1/2, c-Jun N-terminal kinase (JNK), p38 MAPK, and NF-κB signaling pathways in OBA-9 cells. In addition, the stimulator of interferon genes (STING), an essential innate immune signaling molecule, was triggered by a cytosolic pathogen DNA. Pg -OMV-induced IL-6 and IL-8 mRNA expression and production were significantly suppressed by STING-specific small interfering RNA. Taken together, these results demonstrated that Pg -OMV-activated Erk1/2, JNK, p38 MAPK, STING, and NF-κB signaling pathways resulting in increased IL-6 and IL-8 expression in human gingival epithelial cells. These results suggest that Pg -OMVs may play important roles in periodontitis exacerbation by stimulating various pathways.
Keyphrases
- signaling pathway
- pi k akt
- induced apoptosis
- nuclear factor
- oxidative stress
- epithelial mesenchymal transition
- endothelial cells
- toll like receptor
- diabetic rats
- lps induced
- anti inflammatory
- chronic obstructive pulmonary disease
- drug induced
- cell cycle arrest
- dendritic cells
- intensive care unit
- candida albicans
- immune response
- circulating tumor
- extracorporeal membrane oxygenation
- mass spectrometry
- long non coding rna
- protein kinase
- stress induced