Lee Dahae, Kim Yejin, Jo Hyejung, Go Cheolhyeon, Jeong Yoojin, Jang Yoojin, Kang Dongmin, Park Kwanjin, Kim Yoon-Seong, Kang Jae Seung
Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
Medical Research Center, Institute of Allergy and Clinical Immunology, Seoul National University, Seoul 03080, Korea.
Antioxidants (Basel). 2021 Jun 11;10(6):945. doi: 10.3390/antiox10060945.
Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by eczemous lesions on the skin that manifest as severe itching and last a long time. AD is thought to be a response to local allergens, including house dust mites (HDMs). Aptamin C is a modified form of vitamin C comprised of aptamers (DNA fragments) that bind specifically to vitamin C and inhibit its oxidation, thereby increasing its stability and antioxidant effects. It is already known that vitamin C shows an anti-inflammatory effect on skin inflammation. Oxidative stress is one of the major causes of inflammatory diseases, including HDM-induced skin inflammation, suggesting that the antioxidant activity of Aptamin C could regulate inflammatory responses to HDMs in the skin keratinocyte cell line HaCaT and primary skin keratinocytes. Aptamin C not only inhibited HDM-induced proliferation of both type of cells, but suppressed HDM-induced increases in interleukin (IL)-1α and IL-6 production by these cells. In addition, Aptamin C suppressed the production of IL-17 and IL-22 by T cells, which are closely associated with AD pathogenesis, as well as HDM-induced IL-22Rα expression. Aptamin C also reduced the production of thymus and activation-regulated chemokine (TARC) by suppressing the interaction between IL-22 and IL-22Rα, as well as reducing T cell migration. Although HDM treatment markedly increased the expression of glial cell line-derived neurotrophic factor (GDNF), which is associated with itching in AD skin lesions, this increase was reduced by Aptamin C treatment. Taken together, these results suggest that Aptamin C can effectively regulate inflammatory lesions, such as AD, by regulating the production of inflammatory cytokines and GDNF induced by HDM.
特应性皮炎(AD)是一种慢性炎症性皮肤病,其特征是皮肤上出现湿疹样病变,表现为剧烈瘙痒且持续时间长。AD被认为是对包括屋尘螨(HDM)在内的局部过敏原的一种反应。Aptamin C是维生素C的一种修饰形式,由适体(DNA片段)组成,这些适体特异性结合维生素C并抑制其氧化,从而提高其稳定性和抗氧化作用。已知维生素C对皮肤炎症具有抗炎作用。氧化应激是包括HDM诱导的皮肤炎症在内的炎症性疾病的主要原因之一,这表明Aptamin C的抗氧化活性可能调节皮肤角质形成细胞系HaCaT和原代皮肤角质形成细胞对HDM的炎症反应。Aptamin C不仅抑制HDM诱导的这两种细胞的增殖,还抑制HDM诱导的这些细胞中白细胞介素(IL)-1α和IL-6的产生增加。此外,Aptamin C抑制与AD发病机制密切相关的T细胞产生IL-17和IL-22,以及HDM诱导的IL-22Rα表达。Aptamin C还通过抑制IL-22与IL-22Rα之间的相互作用以及减少T细胞迁移,降低了胸腺和活化调节趋化因子(TARC)的产生。尽管HDM处理显著增加了与AD皮肤病变瘙痒相关的胶质细胞源性神经营养因子(GDNF)的表达,但Aptamin C处理可降低这种增加。综上所述,这些结果表明Aptamin C可以通过调节HDM诱导的炎性细胞因子和GDNF的产生,有效调节诸如AD等炎性病变。