Abstract
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.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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This work was supported by grants from the National Natural Science Foundation of China (Funding No. 81870770 and 82170959).
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All authors contributed extensively to the work presented in this paper. Y.H. and L.Z. conceived and designed the study. L.Z. and C.Z. completed most of the animal experiments. Y.H. and L.T. carried out cellular experiments. X.L. and P.W. analyzed the data. Y.H. wrote the original draft. L.G. and C.Z. reviewed and edited the manuscript. All authors have reviewed the final version of the manuscript and approved its submission for publishing.
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Animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC), Sun Yat-sen University, Guangzhou, Guangdong, China (SYSU-IACUC-2021-000545). The human tissues we used were collected in the Hospital of Stomatology of Sun Yat-sen University, and the use of human tissues was approved by the Medical Ethics Committee of Hospital of Stomatology of Sun Yat-sen University (KQEC-2022-38-01). The study was performed in line with the principles of the Declaration of Helsinki.
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Huang, Y., Zhang, L., Tan, L. et al. Interleukin-22 Inhibits Apoptosis of Gingival Epithelial Cells Through TGF-β Signaling Pathway During Periodontitis. Inflammation 46, 1871–1886 (2023). https://doi.org/10.1007/s10753-023-01847-w
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DOI: https://doi.org/10.1007/s10753-023-01847-w