Topical anti-TNF-a ssDNA aptamer decreased the imiquimod induced psoriatic inflammation in BALB/c mice.
Animals
Mice
Imiquimod
/ therapeutic use
Interleukin-17
/ genetics
Tumor Necrosis Factor Inhibitors
/ adverse effects
Mice, Inbred BALB C
DNA, Single-Stranded
/ metabolism
Psoriasis
/ chemically induced
Inflammation
/ pathology
Tumor Necrosis Factor-alpha
/ metabolism
RNA, Messenger
/ metabolism
Disease Models, Animal
Skin
/ metabolism
Aptamer
IL-17A
Imiquimod
Inflammation
Psoriasis
TNF-ɑ
Journal
Cytokine
ISSN: 1096-0023
Titre abrégé: Cytokine
Pays: England
ID NLM: 9005353
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
19
08
2023
revised:
08
10
2023
accepted:
19
10
2023
medline:
10
11
2023
pubmed:
25
10
2023
entrez:
25
10
2023
Statut:
ppublish
Résumé
Tumor Necrosis Factor-α (TNF-α) 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-α factors instead of usual anti-TNF-α monoclonal antibodies. Compared to antibodies, single-stranded DNA or RNA molecules named aptamers, have advantages such as time-saving, less risk for immunogenicity and cost-effectiveness. Therefore, the aim of the present study was to assess the therapeutic effects of T1-T4 dimer anti-TNF-ɑ ssDNA aptamer topical treatment in the imiquimod (IMQ)-induced psoriasis animal model. 5% IMQ cream was prescribed on the right ear of BALB/c to induce psoriasis model. The hydrogel-containing anti-TNF-ɑ 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-1β, STAT3, and S100a9, were evaluated in mice treated ear with quantitative Real Time-PCR. The anti-TNF-ɑ 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). According to our findings, this aptamer seems to be a prospective candidate for treating psoriatic inflammation especially in lower concentrations.
Sections du résumé
BACKGROUND
BACKGROUND
Tumor Necrosis Factor-α (TNF-α) 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-α factors instead of usual anti-TNF-α monoclonal antibodies. Compared to antibodies, single-stranded DNA or RNA molecules named aptamers, have advantages such as time-saving, less risk for immunogenicity and cost-effectiveness. Therefore, the aim of the present study was to assess the therapeutic effects of T1-T4 dimer anti-TNF-ɑ ssDNA aptamer topical treatment in the imiquimod (IMQ)-induced psoriasis animal model.
METHODS
METHODS
5% IMQ cream was prescribed on the right ear of BALB/c to induce psoriasis model. The hydrogel-containing anti-TNF-ɑ 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-1β, STAT3, and S100a9, were evaluated in mice treated ear with quantitative Real Time-PCR.
RESULTS
RESULTS
The anti-TNF-ɑ 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
CONCLUSIONS
According to our findings, this aptamer seems to be a prospective candidate for treating psoriatic inflammation especially in lower concentrations.
Identifiants
pubmed: 37879125
pii: S1043-4666(23)00284-3
doi: 10.1016/j.cyto.2023.156406
pii:
doi:
Substances chimiques
Imiquimod
P1QW714R7M
Interleukin-17
0
Tumor Necrosis Factor Inhibitors
0
DNA, Single-Stranded
0
Tumor Necrosis Factor-alpha
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
156406Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.