Icariin represses the inflammatory responses and survival of rheumatoid arthritis fibroblast-like synoviocytes by regulating the TRIB1/TLR2/NF-kB pathway.
Int Immunopharmacol
; 110: 108991, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35792272
BACKGROUND: Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis. METHODS: qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes. RESULTS: Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1. CONCLUSIONS: Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Sinoviocitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2022
Tipo del documento:
Article
Pais de publicación:
Países Bajos