Icariin restrains NLRP3 inflammasome-mediated Th2 immune responses and ameliorates atopic dermatitis through modulating a novel lncRNA MALAT1/miR-124-3p axis.
Pharm Biol
; 61(1): 1249-1259, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37602424
ABSTRACT
CONTEXT Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. OBJECTIVE:
The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. MATERIALS ANDMETHODS:
BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin.RESULTS:
Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. DISCUSSION ANDCONCLUSIONS:
The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Dermatite Atópica
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China