Full Papers
Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study
R. Kong1, J. Gao2, L. Ji3, Y. Peng4, J. Zhang5, D. Zhao6
- Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
- Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
- Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
- Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
- Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
- Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China. dongbaozhao@163.com
CER13047
2021 Vol.39, N°2
PI 0289, PF 0303
Full Papers
PMID: 32662411 [PubMed]
Received: 23/12/2019
Accepted : 07/04/2020
In Press: 10/07/2020
Published: 09/04/2021
Abstract
OBJECTIVES:
This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model.
METHODS:
RA-FLS was isolated from knee synovial tissue of an active RA patient. In vitro, the effect of miR-146a mimic/inhibition on RA-FLS functions was investigated. Then the effect of Iguratimod on cell viability, proliferation, apoptosis, migration, invasion, inflammatory cytokines, miR-146a and its downstream gene/pathway in RA-FLS was evaluated. In vivo, the collagen induced arthritis (CIA) rat model was constructed, then the effects of iguratimod, miR-146a inhibition and their combination on treating CIA rat were assessed.
RESULTS:
Iguratimod treatment increased miR-146a while decreased cell proliferation, IRAK1 and TRAF6/JNK1 pathway in RA-FLS in a dose-dependent manner. Notably, iguratimod treatment repressed cell proliferation, migration, invasion, TNF-α, IL-1β, IL-6, IL-17, IRAK1 and TRAF6/JNK1 pathway in RA-FLS, while miR-146a inhibition alleviated the abovementioned effects of Iguratimod on RA-FLS. The in vivo experiments disclosed that iguratimod reduced systemic arthritis score, and decreased TNF-α, IL-1β, IL-6, IL-17, IRAK1 as well as TRAF6/JNK1 pathway, while enhanced apoptosis in synovial tissue of CIA rat model; and in miR-146a inhibition treated CIA rat model, the effect of iguratimod was diminished.
CONCLUSIONS:
Iguratimod ameliorates RA progression via regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway.
