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| Significance and detection of the mitochondrial DNA in peripheral blood from patients with psoriasis vulgaris |
| CAO Yang1, SHEN Yuhong2, SONG Shishen2, QIAN Qing2 |
(1. Department of Laboratory Medicine, Yancheng NO.1 People′s Hospital, Yancheng Jiangsu 224006； 2. Department of Dermatology, Peking Hepingli Hospital, Beijing 100013, China)
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Abstract Objective： To investigate the level of mitochondrial DNA (mtDNA) in peripheral blood of patients with psoriasis vulgaris and its mechanism in the disease. Methods： The peripheral blood of 28 patients with psoriasis vulgaris and 28 healthy controls were collected, and the plasma mtDNA level was detected by quantitative real-time PCR (qRT-PCR). The peripheral blood mononuclear cells (PBMCs) were isolated, and the mRNA expression levels of cyclic GMPAMP synthase (cGAS) and stimulator of interferon gene (STING) were detected by qRT-PCR. PBMCs were co-cultured with mtDNA, and the concentrations of interleukin (IL)-23, IL-17 and interferon (IFN)-γ in the supernatant were detected by enzyme-linked immunosorbent assay. Results： Compared with the healthy group, the mtDNA expression in the peripheral blood of the psoriasis group was significantly increased ［(2.34±0.81) vs (1.18±0.25), P<0.001］, and was positively correlated with the psoriasis area and severity index (PASI) score (r=0.693, P<0.001). Compared with the healthy group, the levels of cGAS and STING mRNA in PBMCs of the psoriasis group were significantly increased (both P<0.001). The concentrations of IL-23, IL-17 and IFN-γ in the supernatant of PBMCs cocultured with mtDNA were significantly higher than those in the blank control group (all P<0.001) and positively correlated with PASI score (r=0.647, 0.585, 0.492, all P<0.01). Conclusion： The mtDNA in peripheral blood of patients with psoriasis is abnormally elevated and may participate in the process of psoriasis by activating cGAS/STING signaling pathway in immune cells.
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Received: 19 September 2022
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［1］KulawikPióro A, Miastkowska M. Polymeric gels and their application in the treatment of psoriasis vulgaris: a review［J］. Int J Mol Sci, 2021, 22(10): 5124-5132.
［2］Kono F, Honda T, Aini W, et al. Interferonγ/CCR5 expression in invariant natural killer T cells and CCL5 expression in capillary veins of dermal papillae correlate with development of psoriasis vulgaris［J］. Br J Dermatol, 2014, 170(5): 1048-1055.
［3］Zhou L, Zhang YF, Yang FH, et al. Mitochondrial DNA leakage induces odontoblast inflammation via the cGASSTING pathway［J］. Cell Commun Signal, 2021, 19(1): 58-70.
［4］中华医学会皮肤性病学分会银屑病专业委员会. 中国银屑病诊疗指南(2018完整版)［J］. 中华皮肤科杂志, 2019, 52(10): 667-710。
［5］Albanesi C, Madonna S, Gisondi P, et al. The interplay between keratinocytes and immune cells in the pathogenesis of psoriasis［J］. Front Immunol, 2018, 9: 1549-1561.
［6］Tokuyama M, Mabuchi T. New treatment addressing the pathogenesis of psoriasis［J］. Int J Mol Sci, 2020, 21(20): 7488.
［7］Grn F, Kerstan A, Serfling E, et al. Current developments in the immunology of psoriasis［J］. Yale J Biol Med, 2020, 93(1): 97-110.
［8］袁清, 刘江华, 曾召林. 线粒体功能障碍在代谢性炎症中的作用［J］. 江苏大学学报(医学版), 2021, 31(5): 448-454.
［9］Rusecka J, Kaliszewska M, Bartnik E, et al. Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA［J］. J Appl Genet, 2018, 59(1): 43-57.
［10］Therianou A, Vasiadi M, Delivanis DA, et al. Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis［J］. Exp Dermatol, 2019, 28(1): 72-75.
［11］Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury［J］. Nature, 2010, 464(7285): 104-107.
［12］Willemsen J, Neuhoff MT, Hoyler T, et al. TNF leads to mtDNA release and cGAS/STINGdependent interferon responses that support inflammatory arthritis［J］. Cell Rep, 2021, 37(6): 109977.
［13］Riley JS, Tait SW. Mitochondrial DNA in inflammation and immunity［J］. EMBO Rep, 2020, 21(4): e49799.
［14］Cao DJ, Schiattarella GG, Villalobos E, et al. Cytosolic DNA sensing promotes macrophage transformation and governs myocardial ischemic injury［J］. Circulation, 2018, 137(24): 2613-2634.
［15］Kerur N, Fukuda S, Banerjee D, et al. cGAS drives noncanonicalinflammasome activation in agerelated macular degeneration［J］. Nat Med, 2018, 24(1): 50-61.
［16］Kurtovic NO, Halilovic EK. Serum concentrations of interferon gamma (IFNγ) in patients with psoriasis: correlation with clinical type and severity of the disease［J］. Med Arch, 2018, 72(6): 410-413.
［17］JohnsonHuang LM, SuárezFarias M, Pierson KC, et al. A single intradermal injection of IFNγ induces an inflammatory state in both nonlesional psoriatic and healthy skin［J］. J Investig Dermatol, 2012, 132: 1177-1187.
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. [J]. Journal of Jiangsu University(Medicine Edition), 2023, 33(02): 130-134. |
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