Therapeutic effect and mechanism of CXCR3 inhibitor in rheumatoid arthritis in mice
10.12007/j.issn.0258-4646.2025.09.006
- VernacularTitle:CXCR3抑制剂对小鼠类风湿关节炎的治疗作用及机制
- Author:
Lijing HUANG
1
;
Zicong CHEN
;
Chunchun YANG
;
Yu JING
;
Wenjia NIE
Author Information
1. 河北医科大学第一医院风湿免疫科,石家庄 050030
- Publication Type:Journal Article
- Keywords:
CXCR3 inhibitor;
Th1/Th2 cell ratio;
rheumatoid arthritis;
immunity
- From:
Journal of China Medical University
2025;54(9):796-801
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effect and underlying mechanism of action of a CXCR3 inhibitor in rheumatoid arthritis(RA)in mice model.Methods Thirty BALB/C mice were randomly divided into control,model,and treatment groups.RA model was established in both the model and treatment groups using a collagen induction method.Upon successful modeling,mice in the treat-ment group received a daily oral administration of 1 mg/kg SCH 546738(CXCR3 inhibitor)for 4 weeks,whereas those in the control and model groups received equivalent volumes of saline.During treatment,the weekly arthritis index scores of mice were recorded.The expres-sion of TNF-α,IFN-γ,and IL-1β in joint tissues was determined based on Western blotting and qRT-PCR analyses.In addition,we used flow cytometry to assess peripheral blood Th1/Th2 cell ratios,and serum levels of IFN-γ and IL-4 were measured using ELISA.Peripheral blood CD4+T cells were isolated and co-incubated with SCH 546738,and subsequently assessed as CD4+T and CD4+T+SCH 546738 groups.In addition,Th1/Th2 cell ratios were assessed using flow cytometry.Results Compared with the control group,mice in the model group were characterized by elevated weekly arthritic index scores,increases in the joint tissues expression of TNF-α,IFN-γ,and IL-1β,heightened peripheral blood Th1/Th2 cell ratios,and raised serum IFN-γ levels(P＜0.05).In contrast to the model group,the treatment group mice had lower weekly arthritis index scores,reductions in the joint tissue expression of TNF-α,IFN-γ,and IL-1β,diminished peripheral blood Th1/Th2 cell ratios,and lowered serum IFN-γ levels(P＜0.05).Moreover,compared with the CD4+T group,the CD4+T+SCH 546738 group was characterized reduced Th1/Th2 cell ratios(P＜0.001).Conclusion The CXCR3 inhibitor SCH 546738 can alle-viate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.
