Regulation of oral mucosal immunity in human oral epithelial cells and periodontitis

1.口腔上皮细胞在细胞中组成性表达白细胞介素-18（IL-18）的前体形式。用γ-干扰素（IFN-γ）预处理后，用中性粒细胞丝氨酸蛋白酶、蛋白酶3（PR 3）和脂多糖（LPS）共刺激细胞产生具有生物活性的IL-18。PR 3被发现通过G蛋白偶联蛋白酶激活受体-2.2激活口腔上皮细胞。口腔上皮细胞不表达细菌模式识别受体CD 14，而表达Toll样受体（TLR）/MD-2/MyD 88系统，其在先天免疫识别中是关键的。然而，即使在可溶性CD 14的存在下，细胞对细菌组分也是难治的。细胞能够对来自黑色素细菌（BPB）的组分作出反应。在用IFN-γ引发后，细胞获得对许多细菌组分的反应性。来自BPB的非内毒素糖蛋白以CD 14和TLR 2依赖性方式激活宿主细胞。表达CD 14的人牙龈成纤维细胞（HGF）具有与口腔上皮细胞相同的特性。人牙周膜成纤维细胞（HPLF）表达TLR 2强于HGF。HGF主要对革兰阴性菌起反应，HPLF主要对革兰阳性菌起反应。牙周炎细菌的半胱氨酸蛋白酶（牙龈菌蛋白酶）降解HGF上的CD 14，从而抑制CD 14依赖的对细菌成分的反应性.人唾液腺组成型表达CD 14并在唾液中以可溶形式分泌。

1. Oral epithelial cells constitutively express precursor form of interleukin-18 (IL-18) in the cells. Bioactive IL-18 was produced from the cells on costimulation with neutrophil serine proteinase, proteinase 3 (PR3), and Iipopolysaccharide (LPS) after interferon-γ (IFN-γ)-priming. PR3 was found to activate oral epithelial cells through G protein-coupled protease-activated receptor-2.2. Oral epithelial cells do not express a bacterial pattern recognition receptor, CD 14, and express Toll-like receptors (TLRs)/MD-2/MyD88 system, which is critical in innate immune recognition. However, the cells are refractory to bacterial components even in the presence of soluble CD14, The cells are able to respond to components from black-pigmented bacteria (BPB). The cells acquire responsiveness to many bacterial components after priming with IFN-γ.3. Nonendotoxic glycoprotein from BPB activates host cells in a CD14- and TLR2-dependent manner.4. CD14-expreswsing human gingival fibroblasts (HGF) have the same property with oral epithelial cells. Human periodontal ligament fibroblasts (HPLF) express TLR2 more strongly than HGF. HGF mainly respond to Gram-negative, and HPLF mainly respond to Gram-positive bacterial components, respectively. Cysteine proteinases (gingipains) from periodontopafhic bacteria degrade CD14 on HGF, consequently, suppress CD14-dependent responsiveness to bacterial components.5. Human salivary glands constitutively express CD14 and secrete as a soluble form in saliva.