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Inflammation

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13.06.2023 | RESEARCH

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

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

Erschienen in: Inflammation | Ausgabe 5/2023

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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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Kinane, D.F., P.G. Stathopoulou, and P.N. Papapanou. 2017. Periodontal diseases. Nature Reviews Disease Primers 3: 17038. https://doi.org/10.1038/nrdp.2017.38.CrossRefPubMed

Vitkov, L., J. Singh, C. Schauer, et al. 2023. Breaking the gingival barrier in periodontitis. International Journal of Molecular Sciences 24: 4544. https://doi.org/10.3390/ijms24054544.

Peng X., L. Cheng, Y. You, et al. 2022. Oral microbiota in human systematic diseases. International Journal of Oral Science 14: 14. https://doi.org/10.1038/s41368-022-00163-7.CrossRefPubMedPubMedCentral

Groeger, S. E., and J. Meyle. 2015. Epithelial barrier and oral bacterial infection. Periodontology 2000 69: 46–67. https://doi.org/10.1111/prd.12094.

Zhang, J., L. Cen L, X. Zhang, et al. 2022. MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT. Redox Biology 56: 102469. https://doi.org/10.1016/j.redox.2022.102469.

Listyarifah, D., A. Al-Samadi, A. Salem, et al. 2017. Infection and apoptosis associated with inflammation in periodontitis: An immunohistologic study. Oral Diseases 23: 1144–1154. https://doi.org/10.1111/odi.12711.CrossRefPubMed

Ouyang, W., and A. O’Garra. 2019. IL-10 family cytokines IL-10 and IL-22: From basic science to clinical translation. Immunity 50: 871–891. https://doi.org/10.1016/j.immuni.2019.03.020.CrossRefPubMed

Rutz, S., C. Eidenschenk, and W. Ouyang. 2013. IL-22, not simply a Th17 cytokine. Nature Reviews Immunology 252: 116–132. https://doi.org/10.1111/imr.12027.CrossRef

Guo, X., J. Qiu, T. Tu, et al. 2014. Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection. Immunity 40: 25–39. https://doi.org/10.1016/j.immuni.2013.10.021.CrossRefPubMedPubMedCentral

10.

Alcorn, J.F. 2020. IL-22 plays a critical role in maintaining epithelial integrity during pulmonary infection. Frontiers in Immunology 11: 1160. https://doi.org/10.3389/fimmu.2020.01160.CrossRefPubMedPubMedCentral

11.

Bai, J., J. Bai, and M. Yang. 2021. Interleukin-22 attenuates acute pancreatitis-associated intestinal mucosa injury in mice via STAT3 activation. Gut and Liver 15: 771–781. https://doi.org/10.5009/gnl20210.CrossRefPubMedPubMedCentral

12.

Wang, B., D. Han, F. Li, et al. 2020. Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax. Apoptosis 25: 663–673. https://doi.org/10.1007/s10495-020-01623-3.CrossRefPubMedPubMedCentral

13.

Pan, S., D. Yang, J. Zhang, et al. 2018. Temporal expression of interleukin-22, interleukin-22 receptor 1 and interleukin-22-binding protein during experimental periodontitis in rats. Journal of Periodontal Research 53: 250–257. https://doi.org/10.1111/jre.12512.CrossRefPubMed

14.

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

15.

Dumoutier, L., D. Lejeune, D. Colau, et al. 2001. Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22. Journal of Immunology 166: 7090–7095. https://doi.org/10.4049/jimmunol.166.12.7090.CrossRef

16.

Chen, X., J. Dou, Z. Fu, et al. 2022. Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis. Journal of Applied Oral Science 30: e20220316. https://doi.org/10.1590/1678-7757-2022-0316.

17.

Nadeem, A., N.O. Al-Harbi, M.A. Ansari, et al. 2017. Psoriatic inflammation enhances allergic airway inflammation through IL-23/STAT3 signaling in a murine model. Biochemical Pharmacology 124: 69–82. https://doi.org/10.1016/j.bcp.2016.10.012.CrossRefPubMed

18.

Wang, G., Y. Yu, C. Sun, et al. 2016. STAT3 selectively interacts with Smad3 to antagonize TGF-β signalling. Oncogene 35: 4388–4398. https://doi.org/10.1038/onc.2015.446.CrossRefPubMed

19.

Heldin, C.H., M. Landström, and A. Moustakas. 2009. Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Current Opinion in Cell Biology 21: 166–176. https://doi.org/10.1016/j.ceb.2009.01.021.CrossRefPubMed

20.

Shimoe, M., T. Yamamoto, N. Shiomi, et al. 2014. Overexpression of Smad2 inhibits proliferation of gingival epithelial cells. Journal of Periodontal Research 49: 290–298. https://doi.org/10.1111/jre.12106.CrossRefPubMed

21.

Gu, P., D. Wang, J. Zhang, et al. 2021. Protective function of interleukin-22 in pulmonary fibrosis. Clinical and Translational Medicine 11: e509. https://doi.org/10.1002/ctm2.509.

22.

Polak, D., A. Wilensky, L. Shapira, et al. 2009. Mouse model of experimental periodontitis induced by Porphyromonas gingivalis/Fusobacterium nucleatum infection: Bone loss and host response. Journal of Clinical Periodontology 36: 406–410. https://doi.org/10.1111/j.1600-051X.2009.01393.x.CrossRefPubMed

23.

Graves, D.T., A. Alshabab, M.L. Albiero, et al. 2018. Osteocytes play an important role in experimental periodontitis in healthy and diabetic mice through expression of RANKL. Journal of Clinical Periodontology 45: 285–292. https://doi.org/10.1111/jcpe.12851.CrossRefPubMedPubMedCentral

24.

Gao, L., M. Kang, M.J. Zhang, et al. 2020. Polymicrobial periodontal disease triggers a wide radius of effect and unique virome. npj Biofilms and Microbiomes 6: 10. https://doi.org/10.1038/s41522-020-0120-7.

25.

de Molon, R.S., V.I. Mascarenhas, E.D. de Avila, et al. 2016. Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice. Clinical Oral Investigations 20: 1203–1216. https://doi.org/10.1007/s00784-015-1607-0.CrossRefPubMed

26.

Hu, Z., Y. Chen, M. Gao, et al. 2023. Novel strategy for primary epithelial cell isolation: combination of hyaluronidase and collagenase I. Cell Proliferation 56: e13320. https://doi.org/10.1111/cpr.13320.

27.

Kedjarune, U., S. Pongprerachok, P. Arpornmaeklong, et al. 2001. Culturing primary human gingival epithelial cells: Comparison of two isolation techniques. Journal of cranio-maxillo-facial surgery 29: 224–231. https://doi.org/10.1054/jcms.2001.0229.CrossRefPubMed

28.

Cheng, F., Y. Shen, P. Mohanasundaram, et al. 2016. Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-β-Slug signaling. Proceedings of the National Academy of Sciences of the United States of America 113: E4320–E4327. https://doi.org/10.1073/pnas.1519197113.CrossRefPubMedPubMedCentral

29.

Peng, R.T., Y. Sun, X.D. Zhou, et al. 2022. Treponema denticola promotes OSCC development via the TGF-β signaling pathway. Journal of Dental Research 101: 704–713. https://doi.org/10.1177/00220345211067401.CrossRefPubMed

30.

Velsko, I. M., S. S. Chukkapalli, M. F. Rivera, et al. 2014. Active invasion of oral and aortic tissues by Porphyromonas gingivalis in mice causally links periodontitis and atherosclerosis. PLoS One 9: e97811. https://doi.org/10.1371/journal.pone.0097811.

31.

Yoshimoto, T., T. Fujita, M. Kajiya, et al. 2015. Involvement of smad2 and Erk/Akt cascade in TGF-β1-induced apoptosis in human gingival epithelial cells. Cytokine 75: 165–173. https://doi.org/10.1016/j.cyto.2015.03.011.CrossRefPubMed

32.

Groeger, S., E. Doman, T. Chakraborty, et al. 2010. Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro. European Journal of Oral Sciences 118: 582–589. https://doi.org/10.1111/j.1600-0722.2010.00782.x.CrossRefPubMed

33.

Ebersole, J.L., S.S. Kirakodu, and O.A. Gonzalez. 2021. Oral microbiome interactions with gingival gene expression patterns for apoptosis, autophagy and hypoxia pathways in progressing periodontitis. Immunology 162: 405–417. https://doi.org/10.1111/imm.13292.CrossRefPubMedPubMedCentral

34.

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.

35.

Kinane, J.A., M.R. Benakanakere, J. Zhao, et al. 2012. Porphyromonas gingivalis influences actin degradation within epithelial cells during invasion and apoptosis. Cellular Microbiology 14: 1085–1096. https://doi.org/10.1111/j.1462-5822.2012.01780.x.CrossRefPubMed

36.

Li, S., G. Dong, A. Moschidis, et al. 2013. P. gingivalis modulates keratinocytes through FOXO transcription factors. PLoS One 8: e78541. https://doi.org/10.1371/journal.pone.0078541.

37.

Desta, T., and D.T. Graves. 2007. Fibroblast apoptosis induced by Porphyromonas gingivalis is stimulated by a gingipain and caspase-independent pathway that involves apoptosis-inducing factor. Cellular Microbiology 9: 2667–2675. https://doi.org/10.1111/j.1462-5822.2007.00987.x.CrossRefPubMedPubMedCentral

38.

Sheets, S.M., J. Potempa, J. Travis, et al. 2006. Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial cell adhesion and can induce caspase-independent apoptosis. Infection and Immunity 74: 5667–5678. https://doi.org/10.1128/iai.01140-05.CrossRefPubMedPubMedCentral

39.

Boisvert, H., and M.J. Duncan. 2010. Translocation of Porphyromonas gingivalis gingipain adhesin peptide A44 to host mitochondria prevents apoptosis. Infection and Immunity 78: 3616–3624. https://doi.org/10.1128/iai.00187-10.CrossRefPubMedPubMedCentral

40.

Mao, S., Y. Park, Y. Hasegawa, et al. 2007. Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis. Cellular Microbiology 9: 1997–2007. https://doi.org/10.1111/j.1462-5822.2007.00931.x.CrossRefPubMedPubMedCentral

41.

Stathopoulou, P.G., J.C. Galicia, M.R. Benakanakere, et al. 2009. Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism. BMC Microbiology 9: 107. https://doi.org/10.1186/1471-2180-9-107.CrossRefPubMedPubMedCentral

42.

Qiao, Y.Y., X.Q. Liu, C.Q. Xu, et al. 2016. Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice. World Journal of Gastroenterology 22: 5023–5032. https://doi.org/10.3748/wjg.v22.i21.5023.CrossRefPubMedPubMedCentral

43.

Chen, W., W. Zai, J. Fan, et al. 2020. Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury. Theranostics 10: 5879–5894. https://doi.org/10.7150/thno.43894.CrossRefPubMedPubMedCentral

44.

Wu, Z., Z. Hu, X. Cai, et al. 2017. Interleukin 22 attenuated angiotensin II induced acute lung injury through inhibiting the apoptosis of pulmonary microvascular endothelial cells. Scientific reports 7: 2210. https://doi.org/10.1038/s41598-017-02056-w.CrossRefPubMedPubMedCentral

45.

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.

46.

Qin, X., L. Yuan, H. Ruan, et al. 2019. Interaction of IL-22/IL-22R1 promotes cell proliferation and suppresses apoptosis of colorectal cancer via phosphorylation of STAT3. Biocell 43: 89–98. https://doi.org/10.32604/biocell.2019.06352.

47.

Li, M., D. Wang, J. He, et al. 2020. Bcl-X(L): A multifunctional anti-apoptotic protein. Pharmacological Research 151: 104547. https://doi.org/10.1016/j.phrs.2019.104547.

48.

Youle, R.J., and A. Strasser. 2008. The BCL-2 protein family: Opposing activities that mediate cell death. Nature Reviews Molecular Cell Biology 9: 47–59. https://doi.org/10.1038/nrm2308.CrossRefPubMed

49.

Murad, F., and A.J. Garcia-Saez. 2021. Bcl-xL inhibits tBid and Bax via distinct mechanisms. Faraday Discussions 232: 86–102. https://doi.org/10.1039/d0fd00045k.CrossRefPubMed

50.

Ryter, S.W., H.P. Kim, A. Hoetzel, et al. 2007. Mechanisms of cell death in oxidative stress. Antioxidants and Redox Signaling 9: 49–89. https://doi.org/10.1089/ars.2007.9.49.CrossRefPubMed

51.

Pickert, G., C. Neufert, M. Leppkes, et al. 2009. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. Journal of Experimental Medicine 206: 1465–1472. https://doi.org/10.1084/jem.20082683.CrossRefPubMedPubMedCentral

52.

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.

53.

Brown, K.A., J.A. Pietenpol, and H.L. Moses. 2007. A tale of two proteins: Differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. Journal of Cellular Biochemistry 101: 9–33. https://doi.org/10.1002/jcb.21255.CrossRefPubMed

54.

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.

55.

Zhang, S., C. Li, J. Liu, et al. 2020. Fusobacterium nucleatum promotes epithelial-mesenchymal transition through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway. FEBS Journal 287: 4032–4047. https://doi.org/10.1111/febs.15233.CrossRefPubMed

56.

Lee, J., J.S. Roberts, K.R. Atanasova, et al. 2017. Human primary epithelial cells acquire an epithelial-mesenchymal-transition phenotype during long-term infection by the oral opportunistic pathogen, Porphyromonas gingivalis. Frontiers in cellular and infection microbiology 7: 493. https://doi.org/10.3389/fcimb.2017.00493.CrossRefPubMedPubMedCentral

57.

Saliem, S.S., S.Y. Bede, A.A. Abdulkareem, et al. 2022. Gingival tissue samples from periodontitis patients demonstrate epithelial-mesenchymal transition phenotype. Journal of Periodontal Research 58: 247-255. https://doi.org/10.1111/jre.13086.CrossRefPubMed

58.

Abdulkareem, A.A., R.M. Shelton, G. Landini, et al. 2018. Potential role of periodontal pathogens in compromising epithelial barrier function by inducing epithelial-mesenchymal transition. Journal of Periodontal Research 53: 565–574. https://doi.org/10.1111/jre.12546.CrossRefPubMed

59.

Johnson, J.R., M. Nishioka, J. Chakir, et al. 2013. IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells. Respiratory Research 14: 118. https://doi.org/10.1186/1465-9921-14-118.CrossRefPubMedPubMedCentral

60.

Sisto, M., L. Lorusso, R. Tamma, et al. 2019. Interleukin-17 and -22 synergy linking inflammation and EMT-dependent fibrosis in Sjögren’s syndrome. Clinical and Experimental Immunology 198: 261–272. https://doi.org/10.1111/cei.13337.CrossRefPubMedPubMedCentral

61.

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

62.

Iordanskaia, T., and A. Nawshad. 2011. Mechanisms of transforming growth factor beta induced cell cycle arrest in palate development. Journal Of Cellular Physiology 226: 1415–1424. https://doi.org/10.1002/jcp.22477.CrossRefPubMedPubMedCentral

63.

Buonato, J.M., I.S. Lan, and M.J. Lazzara. 2015. EGF augments TGFbeta-induced epithelial-mesenchymal transition by promoting SHP2 binding to GAB1. Journal of Cell Science 128: 3898–3909. https://doi.org/10.1242/jcs.169599.CrossRefPubMed

64.

Hu, Y., K. He, D. Wang, et al. 2013. TMEPAI regulates EMT in lung cancer cells by modulating the ROS and IRS-1 signaling pathways. Carcinogenesis 34: 1764–1772. https://doi.org/10.1093/carcin/bgt132.CrossRefPubMed

65.

Song, J., and W. Shi. 2018. The concomitant apoptosis and EMT underlie the fundamental functions of TGF-β. Acta Biochimica et Biophysica Sinica 50: 91–97. https://doi.org/10.1093/abbs/gmx117.CrossRefPubMed

Titel: Interleukin-22 Inhibits Apoptosis of Gingival Epithelial Cells Through TGF-β Signaling Pathway During Periodontitis
verfasst von: Yina Huang
Lu Zhang
Lingping Tan
Chi Zhang
Xiting Li
Panpan Wang
Li Gao
Chuanjiang Zhao
Publikationsdatum: 13.06.2023
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 5/2023
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-023-01847-w

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

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