Panahipour Layla, Cervantes Lara Cristina Cunha, Oladzad Abbasabadi Azarakhsh, Sordi Mariane Beatriz, Kargarpour Zahra, Gruber Reinhard
Department of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria.
Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (UNESP), Araçatuba, Sao Paulo 16015-050, Brazil.
Life (Basel). 2022 Jul 13;12(7):1045. doi: 10.3390/life12071045.
Periodontitis is an inflammatory process that is associated with caspase activity. Caspases could thus become molecular targets for the modulation of the inflammatory response to harmful factors, such as lipopolysaccharides (LPS) and TNFα. Here, the impact of the pan-caspase inhibitor Z-VAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoro-methyl ketone) on the modulation of the LPS-induced inflammatory response of murine RAW 264.7 cells and primary macrophages was examined. Moreover, the inflammatory responses of human gingival fibroblasts, HSC2 oral squamous carcinoma cells and murine ST2 mesenchymal fibroblasts when exposed to TNFα were studied. Data showed that Z-VAD-FMK significantly lowered the inflammatory response of RAW 264.7 cells and primary macrophages, as indicated by the expression of IL1 and IL6. In murine ST2 mesenchymal fibroblasts, the TNFα-induced expression of CCL2 and CCL5 was significantly reduced. In human gingival fibroblasts and HSC2 cells, Z-VAD-FMK considerably reduced the TNFα-induced expression of CXCL8 and CXCL10. These findings suggest that pharmacological blocking of caspases in an inflammatory environment lowers the expression of cytokines and chemokines in periodontal cells.
牙周炎是一种与半胱天冬酶活性相关的炎症过程。因此，半胱天冬酶可能成为调节对有害因子（如脂多糖（LPS）和肿瘤坏死因子α（TNFα））炎症反应的分子靶点。在此，研究了泛半胱天冬酶抑制剂Z-VAD-FMK（苄氧羰基-缬氨酰-丙氨酰-天冬氨酰-[O-甲基]-氟甲基酮）对小鼠RAW 264.7细胞和原代巨噬细胞LPS诱导的炎症反应调节的影响。此外，还研究了人牙龈成纤维细胞、HSC2口腔鳞状癌细胞和小鼠ST2间充质成纤维细胞暴露于TNFα时的炎症反应。数据显示，Z-VAD-FMK显著降低了RAW 264.7细胞和原代巨噬细胞的炎症反应，如白细胞介素1（IL1）和白细胞介素6（IL6）的表达所示。在小鼠ST2间充质成纤维细胞中，TNFα诱导的趋化因子配体2（CCL2）和趋化因子配体5（CCL5）的表达显著降低。在人牙龈成纤维细胞和HSC2细胞中，Z-VAD-FMK显著降低了TNFα诱导的CXC趋化因子配体8（CXCL8）和CXC趋化因子配体10（CXCL10）的表达。这些发现表明，在炎症环境中对半胱天冬酶进行药理学阻断可降低牙周细胞中细胞因子和趋化因子的表达。
