Kim Moon-Soo, Yun Jeong-Won, Park Jin-Ho, Park Bong-Wook, Kang Young-Hoon, Hah Young-Sool, Hwang Sun-Chul, Woo Dong Kyun, Byun June-Ho
1. Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Chilam-dong, Jinju, 660-702, Republic of Korea.
2. Clinical Research Institutue of Gyeongsang National University Hospital, Jinju, Republic of Korea.
Int J Med Sci. 2016 Apr 27;13(5):357-64. doi: 10.7150/ijms.14592. eCollection 2016.
The deleterious role of cigarette smoke has long been documented in various human diseases including periodontal complications. In this report, we examined this adverse effect of cigarette smoke on human gingival fibroblasts (HGFs) which are critical not only in maintaining gingival tissue architecture but also in mediating immune responses. As well documented in other cell types, we also observed that cigarette smoke promoted cellular reactive oxygen species in HGFs. And we found that this cigarette smoke-induced oxidative stress reduced HGF viability through inducing apoptosis. Our results indicated that an increased Bax/Bcl-xL ratio and resulting caspase activation underlie the apoptotic death in HGFs exposed to cigarette smoke. Furthermore, we detected that cigarette smoke also triggered autophagy, an integrated cellular stress response. Interesting, a pharmacological suppression of the cigarette smoke-induced autophagy led to a further reduction in HGF viability while a pharmacological promotion of autophagy increased the viability of HGFs with cigarette smoke exposures. These findings suggest a protective role for autophagy in HGFs stressed with cigarette smoke, highlighting that modulation of autophagy can be a novel therapeutic target in periodontal complications with cigarette smoke.
长期以来,香烟烟雾的有害作用在包括牙周并发症在内的各种人类疾病中都有记载。在本报告中,我们研究了香烟烟雾对人牙龈成纤维细胞(HGFs)的这种不良影响,人牙龈成纤维细胞不仅在维持牙龈组织结构方面至关重要,而且在介导免疫反应方面也起着关键作用。正如在其他细胞类型中所充分证明的那样,我们还观察到香烟烟雾会促进HGFs中的细胞活性氧生成。并且我们发现这种香烟烟雾诱导的氧化应激通过诱导细胞凋亡降低了HGF的活力。我们的结果表明,Bax/Bcl-xL比值增加以及由此导致的半胱天冬酶激活是暴露于香烟烟雾中的HGFs凋亡死亡的基础。此外,我们检测到香烟烟雾还引发了自噬,这是一种综合的细胞应激反应。有趣的是,对香烟烟雾诱导的自噬进行药理学抑制会导致HGF活力进一步降低,而药理学促进自噬则会增加暴露于香烟烟雾中的HGFs的活力。这些发现表明自噬在受到香烟烟雾应激的HGFs中具有保护作用,突出了自噬调节可能成为香烟烟雾所致牙周并发症的一种新型治疗靶点。