Huang Yina, Zhang Lu, Tan Lingping, Zhang Chi, Li Xiting, Wang Panpan, Gao Li, Zhao Chuanjiang
Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, No.56, Lingyuanxi Road, Yuexiu District, Guangzhou, 510055, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
Inflammation. 2023 Oct;46(5):1871-1886. doi: 10.1007/s10753-023-01847-w. Epub 2023 Jun 13.
Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth-supporting tissues. The gingival epithelium is the first barrier of periodontal tissue against oral pathogens and harmful substances. The structure and function of epithelial lining are essential for maintaining the integrity of the epithelial barrier. Abnormal apoptosis can lead to the decrease of functional keratinocytes and break homeostasis in gingival epithelium. Interleukin-22 is a cytokine that plays an important role in epithelial homeostasis in intestinal epithelium, inducing proliferation and inhibiting apoptosis, but its role in gingival epithelium is poorly understood. In this study, we investigated the effect of interleukin-22 on apoptosis of gingival epithelial cells during periodontitis. Interleukin-22 topical injection and Il22 gene knockout were performed in experimental periodontitis mice. Human gingival epithelial cells were co-cultured with Porphyromonas gingivalis with interleukin-22 treatment. We found that interleukin-22 inhibited apoptosis of gingival epithelial cells during periodontitis in vivo and in vitro, decreasing Bax expression and increasing Bcl-xL expression. As for the underlying mechanisms, we found that interleukin-22 reduced the expression of TGF-β receptor type II and inhibited the phosphorylation of Smad2 in gingival epithelial cells during periodontitis. Blockage of TGF-β receptors attenuated apoptosis induced by Porphyromonas gingivalis and increased Bcl-xL expression stimulated by interleukin-22. These results confirmed the inhibitory effect of interleukin-22 on apoptosis of gingival epithelial cells and revealed the involvement of TGF-β signaling pathway in gingival epithelial cell apoptosis during periodontitis.
牙周炎是一种以牙齿支持组织破坏为特征的慢性炎症性疾病。牙龈上皮是牙周组织抵御口腔病原体和有害物质的第一道屏障。上皮衬里的结构和功能对于维持上皮屏障的完整性至关重要。异常凋亡可导致功能性角质形成细胞减少并破坏牙龈上皮的稳态。白细胞介素-22是一种细胞因子，在肠道上皮的上皮稳态中发挥重要作用，可诱导增殖并抑制凋亡，但其在牙龈上皮中的作用尚不清楚。在本研究中，我们调查了白细胞介素-22在牙周炎期间对牙龈上皮细胞凋亡的影响。在实验性牙周炎小鼠中进行白细胞介素-22局部注射和Il22基因敲除。将人牙龈上皮细胞与牙龈卟啉单胞菌共培养并进行白细胞介素-22处理。我们发现白细胞介素-22在体内和体外均可抑制牙周炎期间牙龈上皮细胞的凋亡，降低Bax表达并增加Bcl-xL表达。至于潜在机制，我们发现白细胞介素-22在牙周炎期间可降低牙龈上皮细胞中II型TGF-β受体的表达并抑制Smad2的磷酸化。阻断TGF-β受体可减轻牙龈卟啉单胞菌诱导的凋亡，并增加白细胞介素-22刺激的Bcl-xL表达。这些结果证实了白细胞介素-22对牙龈上皮细胞凋亡的抑制作用，并揭示了TGF-β信号通路参与牙周炎期间牙龈上皮细胞凋亡。
