Toll-like Receptors 與 NOD-like Receptors 於牙周炎 致病機轉所扮演之角色

Abstract

表皮細胞是身體抵擋微生物入侵的第一道防線，而由於先天免疫系統(innate immunity)中一群形態辨識受體(pattern recognition receptor, PRR)的發現，讓我們了解到表皮細胞能夠主動地參與免疫反應。接合表皮為牙周組織中與牙周致病菌直接接觸的細胞之一，然而到目前為止，對於PRR在接合表皮的表現與其在牙周炎致病機轉的角色，仍然知之甚少。本研究旨在探討Toll-like receptors(TLR)與NOD-like receptors(NLR)牙齦組織中的表現分布以及與牙周炎發生的相關性。 本實驗利用免疫組織化學染色的方法，藉由第19型角質蛋白(cytokeratin 19,簡稱為CK19)染色分辨牙齦組織中口腔側表皮(oral epithelium)與接合表皮的位置，以利於觀察人類牙齦炎與牙周炎組織中接合表皮細胞TLR4, TLR9, NALP1和NALP3的表現。染色結果發現，牙齦炎與牙周炎的接合表皮細胞都表現CK19，是屬於分化程度低且具增生能力的細胞；相較於牙齦炎組織，牙周炎組織的接合表皮呈現往底下結締組織入侵增生的形態。觀察TLR4與TLR9染色結果，與CK19有類似的位置分布，表現TLR的細胞分布於在牙齦表皮組織的底層，而表現CK19的接合表皮也有較多細胞表現TLR4與TLR9；而牙周炎組織的接合表皮TLR4與TLR9的表現比牙齦炎組織的接合表皮顯著，同時也有較高比例的表皮細胞發生NF-κBp65的核轉移 (nuclear translocation)。觀察NLR家族的NALP1與NALP3的結果發現，牙齦表皮細胞幾乎不表現NALP1。NALP3在牙齦組織的口腔側表皮中主要是由中間與上層細胞所表現，而接合表皮細胞則幾乎都有NALP3的表現，但是在牙周炎組織與牙齦炎組織的表現並無顯著差異。 實驗結果顯示，不同的PRR在牙齦表皮組織中有不同的表現及位置分布，牙齦表皮細胞表現的TLR可能與表皮細胞的增生及牙齦發炎反應有關。牙周炎組織的表皮有較顯著的TLR4與TLR9表現可能與牙周囊袋的形成及牙周炎發生有關，詳細的機轉則需要更進一步的研究探討。

Epithelial cells are the first line of defense against the invasion of microbes into our body. For the identification of various pattern recognition receptors (PRR) in epithelial cells, they can participate and influence the immune responses to pathogens in addition to acting as physical barriers. Junctional epithelium is one of the earliest cells facing the periodontal pathogens in the periodontium. However, there are few literatures discussing the expression of PRRs in the junctional epithelium the their role in the pathogenesis of periodontitis. Therefore, we attempted to explore the expression and distribution of Toll-like Receptors (TLR) and NOD-like Receptors (NLR) in gingival tissues and analyzed their correlation with the occurrence of periodontitis. In this study, we used immunohistochemical staining of cytokeratin 19 (CK19) to differentiate between junctional epithelium (CK19 positive) and oral epithelium (CK19 negative). Then we analyzed the expression of TLR4, TLR9, NALP1, and NALP3 in human gingivitis and periodontitis tissue samples. TLR4 and TLR9 are expressed in basal cell layers of gingival epithelium. Stronger expression of TLR4 and TLR9 was seen in junctional epithelium of periodontitis tissue samples, in accordance to higher percentage of junctional epithelial cells with nuclear translocation of nuclear factor-kB p65 (NF-kB p65) in them. NALP3 is expressed in intermediate and superficial layers of oral epithelium and in junctional epithelium in both gingivitis and periodontitis tissue samples. NALP1 is not expressed in gingival epithelium, Our results demonstrate that each PRR shows different topology in gingival epithelium and they may operate in tissue homeostasis and inflammation. Further study is needed to clarify the role of TLRs in junctional epithelium in the pathogenesis of periodontitis.