Skip to main content
Top
Published in: Inflammation 5/2023

13-06-2023 | RESEARCH

Interleukin-22 Inhibits Apoptosis of Gingival Epithelial Cells Through TGF-β Signaling Pathway During Periodontitis

Authors: Yina Huang, Lu Zhang, Lingping Tan, Chi Zhang, Xiting Li, Panpan Wang, Li Gao, Chuanjiang Zhao

Published in: Inflammation | Issue 5/2023

Login to get access

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.
Appendix
Available only for authorised users
Literature
14.
go back to reference Kotenko, S.V., L.S. Izotova, O.V. Mirochnitchenko, et al. 2001. Identification of the functional interleukin-22 (IL-22) receptor complex: The IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. Journal of Biological Chemistry 276: 2725–2732. https://doi.org/10.1074/jbc.M007837200.CrossRefPubMed Kotenko, S.V., L.S. Izotova, O.V. Mirochnitchenko, et al. 2001. Identification of the functional interleukin-22 (IL-22) receptor complex: The IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. Journal of Biological Chemistry 276: 2725–2732. https://​doi.​org/​10.​1074/​jbc.​M007837200.CrossRefPubMed
34.
go back to reference Inaba, H., A. Amano, R. J. Lamont, et al. 2018. Cell cycle arrest and apoptosis induced by Porphyromonas gingivalis require Jun N-terminal protein kinase- and p53-mediated p38 activation in human trophoblasts. Infection and Immunity 86: e00923-17. https://doi.org/10.1128/iai.00923-17. Inaba, H., A. Amano, R. J. Lamont, et al. 2018. Cell cycle arrest and apoptosis induced by Porphyromonas gingivalis require Jun N-terminal protein kinase- and p53-mediated p38 activation in human trophoblasts. Infection and Immunity 86: e00923-17. https://​doi.​org/​10.​1128/​iai.​00923-17.
45.
go back to reference Takahashi, J., M. Yamamoto, H. Yasukawa, et al. 2020. Interleukin-22 directly activates myocardial stat3 (signal transducer and activator of transcription-3) signaling pathway and prevents myocardial ischemia reperfusion injury. Journal of the American Heart Association 9: e014814. https://doi.org/10.1161/JAHA.119.014814. Takahashi, J., M. Yamamoto, H. Yasukawa, et al. 2020. Interleukin-22 directly activates myocardial stat3 (signal transducer and activator of transcription-3) signaling pathway and prevents myocardial ischemia reperfusion injury. Journal of the American Heart Association 9: e014814. https://​doi.​org/​10.​1161/​JAHA.​119.​014814.
52.
go back to reference Dong, Y., C. Hu, C. Huang, et al. 2021. Interleukin-22 plays a protective role by regulating the JAK2-STAT3 pathway to improve inflammation, oxidative stress, and neuronal apoptosis following cerebral ischemia-reperfusion injury. Mediators of Inflammation 2021: 6621296. https://doi.org/10.1155/2021/6621296. Dong, Y., C. Hu, C. Huang, et al. 2021. Interleukin-22 plays a protective role by regulating the JAK2-STAT3 pathway to improve inflammation, oxidative stress, and neuronal apoptosis following cerebral ischemia-reperfusion injury. Mediators of Inflammation 2021: 6621296. https://​doi.​org/​10.​1155/​2021/​6621296.
54.
go back to reference Bohn, S., L. Hexemer, Z. Huang, et al. 2023. State- and stimulus-specific dynamics of SMAD signaling determine fate decisions in individual cells. Proceedings of the National Academy of Sciences of the United States of America 120: e2210891120. https://doi.org/10.1073/pnas.2210891120. Bohn, S., L. Hexemer, Z. Huang, et al. 2023. State- and stimulus-specific dynamics of SMAD signaling determine fate decisions in individual cells. Proceedings of the National Academy of Sciences of the United States of America 120: e2210891120. https://​doi.​org/​10.​1073/​pnas.​2210891120.
61.
go back to reference Nicolas, F.J., K. Lehmann, P.H. Warne, et al. 2003. Epithelial to mesenchymal transition in Madin-Darby canine kidney cells is accompanied by down-regulation of Smad3 expression, leading to resistance to transforming growth factor-beta-induced growth arrest. Journal of Biological Chemistry 278: 3251–3256. https://doi.org/10.1074/jbc.M209019200.CrossRefPubMed Nicolas, F.J., K. Lehmann, P.H. Warne, et al. 2003. Epithelial to mesenchymal transition in Madin-Darby canine kidney cells is accompanied by down-regulation of Smad3 expression, leading to resistance to transforming growth factor-beta-induced growth arrest. Journal of Biological Chemistry 278: 3251–3256. https://​doi.​org/​10.​1074/​jbc.​M209019200.CrossRefPubMed
Metadata
Title
Interleukin-22 Inhibits Apoptosis of Gingival Epithelial Cells Through TGF-β Signaling Pathway During Periodontitis
Authors
Yina Huang
Lu Zhang
Lingping Tan
Chi Zhang
Xiting Li
Panpan Wang
Li Gao
Chuanjiang Zhao
Publication date
13-06-2023
Publisher
Springer US
Published in
Inflammation / Issue 5/2023
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-023-01847-w

Other articles of this Issue 5/2023

Inflammation 5/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.