Turkiye Klinikleri Journal of Dental Sciences

.: ORIGINAL RESEARCH
Quantitative Evaluation of NFE2L2/NRF2 and Cytokine Response Induced by Porphyromonas Gingivalis Lipopolysaccharide and Nicotine in a Titanium-Oral Mucosa Model
Porphyromonas Gingivalis Lipopolisakkarit ve Nikotin Tarafından Uyarılan Titanyum-Ağız Mukoza Modelinde NFE2L2/NRF2 ve Sitokin Yanıtının Kantitatif Olarak Değerlendirilmesi
Gökhan KASNAKa , Mervi GÜRSOYb,c, Eija KÖNÖNENa , Erhan FIRATLId , Stina SYRJÄNENb,e, Ulvi Kahraman GÜRSOYb
aİstanbul Kent University Faculty of Dentistry, Department of Periodontology, İstanbul, Türkiye
bTurku University Institute of Dentistry, Department of Periodontology, Turku, Finland
cCity of Turku Social Welfare Division, Department of Oral Health, Turku, Finland
dİstanbul University Faculty of Dentistry, Department of Periodontology, İstanbul, Türkiye
eTurku University Hospital, Clinic of Pathology, Turku, Finland
Turkiye Klinikleri J Dental Sci. 2024;30(4):648-57
doi: 10.5336/dentalsci.2024-103018
Article Language: EN
Full Text
ABSTRACT
 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.

Keywords: Cell culture, three dimensional; keratinocyte; fibroblast; porphyromonas gingivalis lipopolysaccharide; nicotine
ÖZET
 Amaç: Titanyum, peri-implant mukozanın kimyasal ve mikrobiyal uyanlara karşı olan sitokin yanıtını değiştirebilir. Bu çalışmada, organotipik titanyum-ağız mukozası modeli kullanılarak Porphyromonas gingivalis lipopolisakkaridi (Pg LPS) ve nikotine karşı oksidatif direnç yanıtının incelenmesi amaçlanmıştır. Gereç ve Yöntemler: Organotipik model, fibroblast içeren kolajen jelin üzerine gingival keratinositlerin ekilmesini takiben üzerlerine titanyum grade (Ti-Gr) 4, Ti-Gr 5 ve hidroksiapatit disklerin yerleştirilmesi ile oluşturuldu. Uyaran olarak Pg LPS (1 l/mL), nikotin (1,54 mM) veya bileşimleri (Pg LPS+nicotine) modellere uygulandı. Kültür ortamındaki interlökin (IL)-1, IL-1 reseptör antagonisti (IL-1Ra), IL-8, monosit kemoatraktan protein [Monocyte chemoattractant protein-1 (MCP-1)] ve vasküler endotelyal büyüme faktörünü seviyeleri Luminex® xMAPTM yöntemi ile ölçüldü. Kültüre edilen örnekler parafin bloklara alınarak, nükleer faktör, eritroid 2 benzeri 2 (NFE2L2/NRF2), 8-hidroksiguanozin (8-OHdG) ve Parkinsonizm ile ilişkilendirilen deglikaz [Parkinsonism-associated deglycase (PARK7/DJ-1)] protein ekspresyonları immünohistokimya ile analiz edildi. İstatistiksel analiz için tek yönlü varyans analizi ve Tukey's HSD testi kullanıldı. Bulgular: Ti-Gr 4, Ti-Gr 5 ve hidroksiapatit gruplarında, nikotin ve Pg LPS+nikotin IL-1β ve IL-1Ra ekspresyonunu arttırdığı görüldü (p<0,01). Pg LPS tek başına (p<0,01) ve nikotin ile kombinasyon halinde (p=0,021) uygulandığında MCP-1 seviyesinde artış gözlemlenirken, tek başına nikotin varlığında MCP-1 seviyesinde azalma görüldü (p=0,024). Tüm test gruplarında IL-8 konsantrasyonlarının arttığı tespit edildi (p<0,01). Nikotin, Pg LPS veya bunların kombinasyonun uygulandığı tüm gruplarda 8-OHdG ve NFE2L2/NRF2 ait immün boylamalar daha yoğun iken (p<0,01), PARK7/DJ-1eşit düzeyde gözlemlendi (p>0,05). Her hangi bir uyaran olmadığında Ti-Gr 4, Ti-Gr 5 veya hidroksiapatit grupları arasında sitokin seviyeleri ve NFEL2/NRF2, 8-Hidroksideoksiguanozin veya PARK7/DJ-1 immün boyamalarında herhangi bir fark bulunamadı (p>0,05). Sonuç: Organotipik titanyum-ağız mukozası modelinde titanyumun sitokin yanıtı uyarmadığı ve oksidatif direnç moleküllerinin artışına neden olmadığı, ancak Pg LPS, nikotin ve kombinasyonlarının varlığında sitokin yanıtını uyardığı ve oksidatif direnç moleküllerinin ortaya çıkmasına neden olduğu çalışmamızca gösterilmiştir.

Anahtar Kelimeler: Hücre kültürü, üç boyutlu; keratinosit; fibroblast; porphyromonas gingivalis lipopolisakkaridler; nikotin
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Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

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-During various attacks to the website,

-Disruption of the website because of a virus.

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Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

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