Olszewska Berenika, Gleń Jolanta, Zabłotna Monika, Nowicki Roman J, Sokołowska-Wojdyło Małgorzata
Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Mariana Smoluchowskiego Str 17, 80-214, Gdańsk, Poland.
Arch Dermatol Res. 2021 Jan;313(1):25-31. doi: 10.1007/s00403-020-02062-5. Epub 2020 Apr 8.
IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.
白细胞介素-6/信号转导与转录激活因子3（IL-6/STAT3）信号通路被认为在蕈样肉芽肿（CTCL）的发病机制中发挥作用。STAT3信号通路相关基因的多态性可能是CTCL的一个危险因素。然而，IL-6和STAT3的遗传基因多态性在CTCL发病机制中的确切作用仍未完全明确。本研究旨在探讨IL-6细胞因子以及IL-6和STAT3基因多态性是否与CTCL易感性、疾病分期及瘙痒强度相关。我们采用序列特异性引物聚合酶链反应法和酶联免疫吸附测定法，比较了106例CTCL患者和198例对照组中IL-6血清水平以及IL-6和STAT3特定单核苷酸多态性的频率。我们发现，CTCL患者的血清IL-6水平显著高于健康对照组（p < 0.05）。我们还证实，与健康对照组相比，CTCL患者中IL-6的CC基因型和STAT3的GG基因型过表达，且它们增加了恶性肿瘤发生的风险（IL-6的比值比（OR）= 1.8，p = 0.04；STAT3的OR = 2.53，p = 0.0064）。此外，STAT3基因多态性的GG基因型似乎与CTCL患者无瘙痒或轻度瘙痒有关。我们的结果表明，IL-6参与了CTCL的发病机制，但与瘙痒无关。此外，IL-6的CC基因型和STAT3基因的GG基因型可能被视为CTCL发生的危险因素。
