Topical anti-TNF-a ssDNA aptamer decreased the imiquimod induced psoriatic inflammation in BALB/c mice

被引:5
作者
Shobeiri, Saeideh Sadat [1 ]
Dashti, Mohammadreza [1 ]
Pordel, Safoora [1 ]
Rezaee, MohammadAli [1 ,2 ]
Haghnavaz, Navideh [1 ]
Moghadam, Malihe [1 ]
Ansari, Bahareh [1 ]
Sankian, Mojtaba [1 ,3 ]
机构
[1] Mashhad Univ Med Sci, Immunol Res Ctr, Fac Med, Mashhad, Iran
[2] Kurdistan Univ Med Sci, Fac Paramed, Dept Med Lab Sci, Sanandaj, Iran
[3] Mashhad Univ Med Sci, Bu Ali Res Inst, Immunol Res Ctr, Sch Med,Immunobiochem Lab, Mashhad, Iran
关键词
Psoriasis; Aptamer; TNF-alpha; IL-17A; Imiquimod; Inflammation; ALPHA; PATHOGENESIS; ANTIBODIES;
D O I
10.1016/j.cyto.2023.156406
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Tumor Necrosis Factor-alpha (TNF-alpha) is a pro-inflammatory factor that plays a pivotal role in psoriasis. Due to limitations of monoclonal antibody-based therapies, it is needed to discover new anti-TNF-alpha factors instead of usual anti-TNF-alpha monoclonal antibodies. Compared to antibodies, single-stranded DNA or RNA molecules named aptamers, have advantages such as time-saving, less risk for immunogenicity and costeffectiveness. Therefore, the aim of the present study was to assess the therapeutic effects of T1-T4 dimer anti-TNF-alpha ssDNA aptamer topical treatment in the imiquimod (IMQ)-induced psoriasis animal model.Methods: 5% IMQ cream was prescribed on the right ear of BALB/c to induce psoriasis model. The hydrogelcontaining anti-TNF-alpha aptamer or treatment control aptamer (anti- Interleukin (IL)17A) was topically prescribed to the mice's ears 10 min before IMQ cream treatment. The psoriasis area severity index (PASI) score was used to evaluate psoriasis intensity. Histopathology analysis was done for mice ears sections. Mass, size, and cell number of mice spleens were measured. The IL-17 level was determined in culture supernatants of axillary lymph node cells using ELISA. The mRNA expression levels of IL-17A, IL-1 beta, STAT3, and S100a9, were evaluated in mice treated ear with quantitative Real Time-PCR.Results: The anti-TNF-alpha ssDNA aptamer lower doses had significant decrease in IMQ-induced PASI score (p < 0.05). In addition, in these groups, the IL-17A, STAT3, and S100a9 mRNA levels were significantly lower than the IMQ group (p < 0.05).Conclusion: According to our findings, this aptamer seems to be a prospective candidate for treating psoriatic inflammation especially in lower concentrations.
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页数:8
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