Quantitative Evaluation of NFE2L2/NRF2 and Cytokine Response Induced by Porphyromonas Gingivalis Lipopolysaccharide and Nicotine in a Titanium-Oral Mucosa Model




Kasnak, Gökhan; Gürsoy, Mervi; Könönen, Eija; Firatli, Erhan; Syrjänen, Stina; Gürsoy, Ulvi Kahraman

PublisherTurkiye Klinikleri

2024

Türkiye klinikleri diş hekimliği bilimleri

Turkiye Klinikleri Journal of Dental Sciences

30

4

648

657

2146-8966

DOIhttps://doi.org/10.5336/dentalsci.2024-103018

http://doi.org/10.5336/dentalsci.2024-103018

https://research.utu.fi/converis/portal/detail/Publication/458956782

Lehden englanninkielinen nimi: Turkiye Klinikleri Journal of Dental Sciences



Objective: Titanium can alter peri-implant mucosa cytokine response to microbiological and chemical stresses. This work used organotypic titanium-oral mucosa model to evaluate oxidant resistance and cytokine response to Porphyromonas gingivalis lipopolysaccharide (Pg LPS) and nicotine. Material and Methods: Seeding gingival keratinocytes on collagen gels with fibroblasts and adding titanium grade (Ti-Gr) 4, Ti-Gr 5, or hydroxyapatite discs developed an organotypic titanium-oral mucosa model. Pg LPS (1 l/mL), nicotine (1.54 mM), or both were given to the model. The Luminex® xMAPTM technology measured interleukin (IL)-1β, IL-1Ra, IL-8, monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor levels in culture media. Cultured tissues were paraffin-blocked and immunohistochemistry was used to measure nuclear factor erythroid 2 like 2 (NFE2L2/NRF2), 8-hydroxyguanosine (8-OHdG), and Parkinsonism-associated deglycase (PARK7/DJ-1). Statistical analysis included one-way analysis of varianceand Tukey's HSD. Results: Nicotine and Pg LPS+nicotine increased IL-1β and IL-1Ra secretions in Ti-Gr 4, Ti-Gr 5, and hydroxyapatite groups (p<0.01). Pg LPS alone (p<0.01) and in conjunction with nicotine (p=0.021) enhanced MCP-1 production, but nicotine alone lowered it (p=0.024). IL-8 concentrations rose in all test groups (p<0.01). All groups treated with nicotine, LPS, or both showed increased 8-Hydroxydeoxyguanosine and NFE2L2/NRF2 immunostainings (p<0.01), whereas PARK7/DJ-1 expression remained unchanged. When assessed without inducers, Ti-Gr 4, Ti-Gr 5, or hydroxyapatite groups showed no significant variations in cytokine secretion patterns, NFEL2/NRF2, 8-OHdG, or PARK7/DJ-1 immunostainings (p>0.05). Conclusion: Titanium did not affect cytokines or oxidant resistance molecules in our organotypic model without inducers. However, Pg LPS, nicotine, and their mixtures enhance cytokines and oxidative resistance molecules.


Last updated on 2025-27-01 at 20:03