Demirel Kartheyaene Jayaprakash, Neves Guimaraes Alessandra, Demirel Isak
Department of Oral and Maxillofacial Surgery, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, Sweden.
Department of Odontological Research, Public Dental Service, Faculty of Medicine and Health, Örebro University, 701 82 Örebro, Sweden.
Pathogens. 2025 Mar 18;14(3):295. doi: 10.3390/pathogens14030295.
Periodontitis is a chronic inflammatory disease characterized by bacterial infection and immune dysregulation. () is a key pathogen linked to disease progression. Caspase-1 and caspase-4 regulate inflammasome activation and cytokine release, yet their roles in gingival epithelial immunity remain unclear. The aim of this study was to elucidate the involvement of caspase-1 and caspase-4 in regulating the immune response to infection in gingival epithelial cells. Human gingival epithelial cells (Ca9-22) and caspase-1- and caspase-4-deficient cells were infected with for 24 h. Inflammatory mediator release was analyzed using Olink proteomics. Bacterial colonization and invasion were assessed using fluorescence-based assays and gentamicin protection assays. Caspase-1- and caspase-4-deficient cells showed significantly altered cytokine and chemokine profiles after infection with showing reduced IL-17C and IL-18 release. We also found an increased release of TGF-α and LIF from caspase-4-deficient cells, along with elevated levels of the chemokines IL-8, CXCL9, and CXCL10. Additionally, both caspase-1- and caspase-4-deficient cells showed increased bacterial colonization and invasion, particularly in caspase-4-deficient cells. These findings suggest that caspase-1 and caspase-4 play distinct yet essential roles in gingival epithelial immunity, regulating cytokine release, barrier integrity, and defense against colonization.
牙周炎是一种以细菌感染和免疫失调为特征的慢性炎症性疾病。（）是与疾病进展相关的关键病原体。半胱天冬酶-1和半胱天冬酶-4调节炎性小体激活和细胞因子释放，但其在牙龈上皮免疫中的作用仍不清楚。本研究的目的是阐明半胱天冬酶-1和半胱天冬酶-4在调节牙龈上皮细胞对感染的免疫反应中的作用。将人牙龈上皮细胞（Ca9-22）以及半胱天冬酶-1和半胱天冬酶-4缺陷细胞用（）感染24小时。使用Olink蛋白质组学分析炎性介质释放。使用基于荧光的检测方法和庆大霉素保护检测方法评估细菌定植和侵袭。半胱天冬酶-1和半胱天冬酶-4缺陷细胞在感染（）后显示细胞因子和趋化因子谱显著改变，白细胞介素-17C和白细胞介素-18释放减少。我们还发现半胱天冬酶-4缺陷细胞中转化生长因子-α和白血病抑制因子的释放增加，同时趋化因子白细胞介素-8、CXC趋化因子配体9和CXC趋化因子配体10水平升高。此外，半胱天冬酶-1和半胱天冬酶-4缺陷细胞均显示细菌定植和侵袭增加，尤其是在半胱天冬酶-4缺陷细胞中。这些发现表明，半胱天冬酶-1和半胱天冬酶-4在牙龈上皮免疫中发挥着独特而重要的作用，调节细胞因子释放、屏障完整性以及抵御（）定植。
