Vitamin D/VDR Signaling Regulates IL-10 Expression in Macrophages from Oral Lichen Planus

doi:10.13701/j.cnki.kqyxyj.2023.06.014

Abstract

Abstract: Objective: To investigate the regulatory roles of vitamin D and its receptor VDR in the cytokines production in macrophages from oral lichen planus (OLP). Methods: Twenty OLP patients and 20 healthy volunteers were recruited. Macrophages from oral tissues were isolated, and the expressions of cytokines and VDR was detected. IL-10 levels were measured in monocyte-derived macrophages and THP-1 cells overexpressed VDR or treated with vitamin D. The binding of VDR and its element in the promoter region of IL-10 gene was confirmed by ChIP and luciferase report assays. Cytokines levels were detected in OLP macrophages with vitamin D treatment. Results: VDR expression was decreased in OLP macrophages and positively correlated with IL-10 expression. Vitamin D/VDR signaling up-regulated IL-10 levels in monocyte-derived macrophages and THP-1 cells. Mechanistically, VDR was able to interact with its element in the promoter to enhance the transcription of IL-10. Vitamin D increased IL-10 levels and decreased pro-inflammatory cytokines expression in OLP macrophages.Conclusion: Vitamin D/VDR signaling regulates IL-10 transcription to mediate cytokines levels in OLP macrophages.

Key words: oral lichen planus, vitamin D, vitamin D receptor, cytokine, IL-10

GE Xuejun, SUN Zhuo, ZHAO Zhenni, DU Jie. Vitamin D/VDR Signaling Regulates IL-10 Expression in Macrophages from Oral Lichen Planus[J]. Journal of Oral Science Research, 2023, 39(6): 541-546.

References

[1] Zotti F, Nocini R, Capocasale G, et al. Malignant transformation evidences of Oral Lichen Planus: When the time is of the essence [J]. Oral Oncol, 2020, 104:104594.
[2] 汪苑苑,王嘉祺,关晓兵.口腔扁平苔藓感染相关因素的研究进展 [J]. 北京口腔医学,2019,27(4): 232-235.
[3] Gonzalez-Moles MA, Warnakulasuriya S, Gonzalez-Ruiz I, et al. Worldwide prevalence of oral lichen planus: A systematic review and meta-analysis [J]. Oral Dis, 2021, 27(4):813-828.
[4] Brazil JC, Quiros M, Nusrat A, et al. Innate immune cell-epithelial crosstalk during wound repair [J]. J Clin Invest, 2019, 129(8): 2983-2993.
[5] Merry R, Belfield L, McArdle P, et al. Oral health and pathology: a macrophage account [J]. Br J Oral Maxillofac Surg, 2012, 50(1): 2-7.
[6] Yang JY, Zhang J, Lu R, et al. T cell-derived exosomes induced macrophage inflammatory protein-1alpha/beta drive the trafficking of CD8⁺ T cells in oral lichen planus [J]. J Cell Mol Med, 2020, 24(23): 14086-14098.
[7] Ferrisse TM, de Oliveira AB, Palacon MP, et al. The role of CD68⁺ and CD163⁺ macrophages in immunopathogenesis of oral lichen planus and oral lichenoid lesions [J]. Immunobiology, 2021, 226(3): 152072.
[8] Wei Z, Yoshihara E, He NH, et al. Vitamin D switches BAF complexes to protect β cells [J]. Cell, 2018, 173(5): 1135-1149.
[9] Liu W, Chen Y, Golan MA, et al. Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis [J]. J Clin Invest, 2013, 123(9): 3983-3996.
[10] Du J, Gao R, Wang Y, et al. MicroRNA-26a/b have protective roles in oral lichen planus [J]. Cell Death Dis, 2020, 11(1): 15.
[11] van der Meij EH, van der Waal I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications [J]. J Oral Pathol Med, 2003, 32(9): 507-512.
[12] Cheng YS, Rees T, Jordan L, et al. Salivary endothelin-1 potential for detecting oral cancer in patients with oral lichen planus or oral cancer in remission [J]. Oral Oncol, 2011, 47(12): 1122-1126.
[13] Chauss D, Freiwald T, McGregor R, et al. Autocrine vitamin D signaling switches off pro-inflammatory programs of T(H)1 cells [J]. Nat Immunol, 2022, 23(1): 62-74.
[14] Emma LB, Ismailova A, Dimeloe S, et al. Vitamin D and immune regulation: Antibacterial, antiviral, anti-inflammatory [J]. JBMR Plus, 2021, 5(1): e10405.
[15] Chen X, Zhang Z, Sun N, et al. Vitamin D receptor enhances NLRC4 inflammasome activation by promoting NAIPs-NLRC4 association [J]. EMBO Rep, 2022, 23(9): e54611.
[16] Simakou T, Freeburn R, Henriquez FL. Gene expression during THP-1 differentiation is influenced by vitamin D3 and not vibrational mechanostimulation [J]. PeerJ, 2021, 9: e11773.
[17] Zhu X, Zhu Y, Li C, et al. 1,25-Dihydroxyvitamin D regulates macrophage polarization and ameliorates experimental inflammatory bowel disease by suppressing miR-125b [J]. Int Immunopharmacol, 2019, 67: 106-118.
[18] Ge XJ, Wang LX, Li MD, et al. Vitamin D/VDR signaling inhibits LPS-induced IFN and IL-1 in Oral epithelia by regulating hypoxia-inducible factor-1 signaling pathway [J]. Cell Commun Signal, 2019, 17(1):18.
[19] Du J, Li R, Yu F, et al. Experimental study on 1,25(OH)₂D₃ amelioration of oral lichen planus through regulating NF-kappaB signaling pathway [J]. Oral Dis, 2017, 23(6): 770-778.
[20] 杨令云.T淋巴细胞亚群检测在口腔扁平苔藓治疗中的应用价值[J].实用口腔医学杂志,2019,35(3): 424-427.
[21] Zhao B, Li R, Yang F, et al. LPS-induced vitamin D receptor decrease in oral keratinocytes is associated with oral lichen planus [J]. Sci Rep, 2018, 8(1): 763.
[22] Ge X, Wang Y, Xie H, et al. 1,25(OH)₂D₃ blocks IFNbeta production through regulating STING in epithelial layer of oral lichen planus [J]. J Cell Mol Med, 2022, 26(13): 3751-3759.
[23] Grimbaldeston MA, Nakae S, Kalesnikoff J, et al. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B [J]. Nat Immunol, 2007, 8(10): 1095-1104.
[24] Wei W, Sun Q, Deng Y, et al. Mixed and inhomogeneous expression profile of Th1/Th2 related cytokines detected by cytometric bead array in the saliva of patients with oral lichen planus [J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2018, 126(2): 142-151.