目的: 探究硫氧还蛋白(Trx)系统在肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)诱导的银屑病样细胞模型中的表达变化情况,揭示其在细胞模型炎症及氧化损伤过程中的潜在作用。方法: 采用TNF-α诱导人角质形成细胞HaCaT细胞建立银屑病样炎症细胞模型,将HaCaT细胞分为对照组、TNF-α模型组;利用CCK-8法检测细胞增殖率,ELISA法检测炎症因子表达及细胞活性氧(ROS)水平,Western blot法检测硫氧还蛋白-1(Thioredoxin-1, Trx-1)、硫氧还蛋白还原酶(Thioredoxin reductase, TrxR)的蛋白表达。结果: 与对照组比较,TNF-α模型组的TrxR表达下降(P＜0.05);Trx-1表达有下降趋势,但无统计学意义;细胞增殖增加(P＜0.001);炎症介质TNF-α、IL-17、IL-22的表达水平均升高(P＜0.001);细胞ROS水平升高(P＜0.001)。结论: TNF-α可诱导人表皮角质形成细胞的TrxR表达水平降低,同时使表皮角质形成细胞的增殖增加、炎症和氧化应激反应增强,提示Trx系统表达异常可能参与TNF-α诱导的类银屑病样氧化-炎症损伤过程。
Objective: To investigate the expression changes of thioredoxin (Trx) system in tumor necrosis factor-α (TNF-α) -induced psoriasis-like cell model, and to reveal its potential role in inflammation and oxidative damage of cell model. Methods: Human keratinocyte HaCaT cells were induced with TNF-α to establish a psoriasis-like inflammatory cell model. Cells were divided into a control group and a TNF-α model group. The CCK-8 assay was used to detect cell proliferation rate, ELISA was applied to measure inflammatory cytokine expression and cellular reactive oxygen species (ROS) levels, and Western blot was performed to analyze the protein expression of thioredoxin-1 (Trx-1) and thioredoxin reductase (TrxR). Results: Compared with the control group, the expression of TrxR in the TNF-α model group was decreased (P＜0.05); the expression of Trx-1 showed a downward trend, but there was no statistical significance; cell proliferation was increased (P＜0.001); the expression levels of inflammatory mediators TNF-α, IL-17 and IL-22 were increased (P＜0.001); the level of ROS was increased (P＜0.001). Conclusion: TNF-α can induce the decrease of TrxR expression in human epidermal keratinocytes, and increase the proliferation, inflammation and oxidative stress of epidermal keratinocytes, suggesting that abnormal expression of Trx system may be involved in TNF-α-induced psoriasis-like oxidative-inflammatory injury process.
[1] Vaengebjerg S, Skov L, Egeberg A, et al. Prevalence, Incidence, and Risk of Cancer in Patients With Psoriasis and Psoriatic Arthritis: A Systematic Review and Meta-analysis[J]. JAMA Dermatology, 2020, 156(4):421-429.
[2] Parisi R, Iskandar IYK, Kontopantelis E, et al. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study[J]. BMJ (Clinical research ed), 2020, 369:m1590.
[3] Sieminska I, Pieniawska M, Grzywa TM. The Immunology of Psoriasis-Current Concepts in Pathogenesis[J]. Clin Rev Allergy Immunol, 2024, 66(2):164-191.
[4] Tampa M, Mitran MI, Mitran CI, et al. Psoriasis: What Is New in Markers of Disease Severity[J]. Medicina (Kaunas), 2024, 60(2):337.
[5] Jelic MD, Mandic AD, Maricic SM, et al. Oxidative stress and its role in cancer[J]. J Cancer Res Ther, 2021, 17(1):22-28.
[6] Kadam DP, Suryakar AN, Ankush RD, et al. Role of oxidative stress in various stages of psoriasis[J]. Indian J Clin Biochem.2010, 25(4):388-392.
[7] Xinastle-Castillo LO, Landa A. Physiological and modulatory role of thioredoxins in the cellular function[J]. Open Med (Wars), 2022, 17(1):2021-2035.
[8] Griffiths CEM, Armstrong AW, Gudjonsson JE, et al. Psoriasis[J]. Lancet, 2021, 397(10281):1301-1315
[9] Kiafar B, Binabaj MM, Jafarian AH, et al. The Relationship between Tissue Thioredoxin Reductase Activity and the Psoriasis Area and Severity Index[J]. Indian J Dermatol, 2020, 65(1):29-32.
[10] Leone GM, Mangano K, Petralia MC, et al. Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy[J]. J Clin Med, 2023, 12(4):1630.
[11] Jang DI, Lee AH, Shin HY, et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics[J]. Int J Mol Sci, 2021, 22(5):2719.
[12] Surh YJ, Chun KS, Cha HH, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation[J]. Mutat Res, 2001, 480-481:243-268.
[13] Yoo MH, Carlson BA, Gladyshev VN, et al. Abrogated thioredoxin system causes increased sensitivity to TNF-α-induced apoptosis via enrichment of p-ERK 1/2 in the nucleus[J]. PloS One, 2013, 8(9):e71427.
[14] Yeo EJ, Shin MJ, Yeo HJ, et al. Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling[J]. Exp Ther Med, 2021, 22(6):1395.
[15] Torres T, Puig L, Vender R, et al. Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study[J]. Am J Clin Dermatol, 2021, 22(4):567-579.
[16] Nerviani A, Boutet MA, Tan WSG, et al. IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors[J]. Ann Rheum Dis, 2021, 80(5):591-597.
