人源胱天蛋白酶-4在受牙周炎影响的牙龈上皮中的表达：其在牙龈卟啉单胞菌挑战的牙龈上皮细胞中的作用。
Expression of human caspase-4 in the gingival epithelium affected with periodontitis: Its involvement in Porphyromonas gingivalis-challenged gingival epithelial cells.
机构信息
Department of Restorative Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand; Oral Biology Research Unit, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand; Research Group of Chronic Inflammatory Oral Diseases and Systemic Disease Associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
出版信息
Arch Oral Biol. 2022 Aug;140:105466. doi: 10.1016/j.archoralbio.2022.105466. Epub 2022 May 24.
OBJECTIVE
Implication of human caspase-4 in periodontitis and in sensing periodontal pathogens by gingival epithelial cells (GECs) is unclear. This study aimed to determine caspase-4 and interleukin (IL)-18 expressions in gingival tissues affected with periodontitis and to investigate caspase-4 involvement in mediating innate immune responses in GECs.
DESIGN
Ex vivo, caspase-4 and IL-18 expressions in gingival biopsies, obtained from healthy participants with periodontitis or clinically healthy gingiva (N = 20 each), were determined by immunohistochemistry. In vitro, caspase-4 activation in cultured GECs stimulated with Porphyromonas gingivalis or Fusobacterium nucleatum was analyzed by immunoblotting. mRNA expressions of human β-defensin-2 (hBD-2), IL-8, and IL-18 in stimulated GECs in the presence or absence of a caspase-4 inhibitor were assayed by RT-qPCR.
RESULTS
Ex vivo, compared with healthy gingival epithelium, the epithelium affected with periodontitis displayed a significant decrease in caspase-4 expression (P = 0.015), whereas IL-18 expression was significantly increased (P = 0.012). Moreover, the expression of caspase-4, but not IL-18, was found to be a predictor of periodontitis (P = 0.007). In vitro, caspase-4 was activated in cultured GECs challenged with P. gingivalis, but not F. nucleatum. mRNA upregulations of hBD-2, IL-8, and IL-18 upon P. gingivalis stimulation were significantly reduced when caspase-4 was inhibited (P < 0.05), whereas the inhibitor failed to suppress those inductions by F. nucleatum.
CONCLUSIONS
Caspase-4 expression is diminished in the epithelium affected with periodontitis while that of IL-18 is enhanced. Caspase-4 activation in P. gingivalis-infected GECs upregulates the three innate immune effector molecules, suggesting a possible sensing mechanism of caspase-4 in GECs in periodontal disease pathogenesis.
目的
人源胱天蛋白酶-4（caspase-4）在牙周炎中的作用及其在牙龈上皮细胞（GECs）中感知牙周病原体的作用尚不清楚。本研究旨在确定牙周炎牙龈组织中 caspase-4 和白细胞介素（IL）-18 的表达，并探讨 caspase-4 介导 GECs 固有免疫反应的作用。
设计
采用免疫组织化学法检测来自牙周炎或临床健康牙龈（各 20 例）的健康参与者牙龈活检组织中 caspase-4 和 IL-18 的表达。体外分析牙龈上皮细胞（GECs）在牙龈卟啉单胞菌或核梭杆菌刺激下 caspase-4 的激活情况。采用 RT-qPCR 检测存在或不存在 caspase-4 抑制剂时，刺激 GECs 中人类β防御素-2（hBD-2）、IL-8 和 IL-18 的 mRNA 表达。
结果
与健康牙龈上皮相比，牙周炎上皮组织中 caspase-4 的表达显著降低（P=0.015），而 IL-18 的表达显著升高（P=0.012）。此外，caspase-4 的表达而不是 IL-18 的表达被发现是牙周炎的预测因素（P=0.007）。体外，牙龈卟啉单胞菌刺激可激活培养的 GECs 中的 caspase-4，但核梭杆菌刺激则不能。当抑制 caspase-4 时，牙龈卟啉单胞菌刺激引起的 hBD-2、IL-8 和 IL-18 的 mRNA 上调显著降低（P<0.05），而抑制剂未能抑制核梭杆菌引起的这些诱导。
结论
牙周炎上皮组织中 caspase-4 的表达减少，而 IL-18 的表达增加。牙龈卟啉单胞菌感染的 GECs 中 caspase-4 的激活上调了这三种固有免疫效应分子，提示 caspase-4 在牙周病发病机制中 GECs 中可能存在一种感应机制。
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