Objective: To explore whether triptolide can alleviate the disease by reducing the infiltration of neutrophils in the joint cavity of collagen-induced arthritis (CIA) mice, and to analyze whether triptolide can reduce the formation of neutrophil extracellular capture networks (NETs) in patients with rheumatoid arthritis (RA) and its mechanism of action, so as to provide theoretical support for the clinical application of tripterygium glycosides in RA. Methods: The core targets of Tripterygium wilfordii intervention in RA disease were explored by using the public database of network medicine. After the CIA model was constructed using DBA1 mice, triptolide was given for 60 days. The hind limbs of the mice were collected for HE staining and the degree of inflammatory cell infiltration in the joint cavity of the mice was observed. Neutrophils in peripheral blood of RA patients were collected and stimulated with triptolide for 2 h. The formation of NETs was observed by immunofluorescence staining. Treatment with triptolide in RA group and triptolide could alleviate joint swelling in CIA mice; triptolide could also inhibit the formation of NETs in peripheral blood neutrophils of RA patients. Transcriptome sequencing was performed on neutrophils in RA group and Tripterygium wilfordii treatment group. Results: Through network pharmacology analysis, PPI protein interaction was performed on the locked overlapping genes, and KEGG and GO analysis were performed. It was found that IL-17, TNF signaling pathway and apoptosis-related pathway were closely related to RA disease. In vivo experiments showed that 389 differential genes were screened from the transcriptome sequencing results of the triptolide treatment group. The GO and KEGG pathways were mainly enriched in JAK-STAT, TNF, and PI3K-Akt signaling pathways. Conclusion: Triptolide can alleviate joint swelling in CIA mice by down-regulating neutrophil infiltration in the joint cavity of CIA mice, and triptolide can reduce the formation of NETs in peripheral blood of RA.This phenomenon may be related to JAK-STAT signaling pathway, TNF signaling pathway, PI3K-Akt and other signaling pathways.
LIU Pengyuan
,
SANG Yali
,
BAI Li
,
WANG Yongfu
. Triptolide affects the progression of rheumatoid arthritis by interfering with neutrophils[J]. Journal of Baotou Medical College, 2025
, 41(3)
: 30
-35
.
DOI: 10.16833/j.cnki.jbmc.2025.03.006
[1] Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative [J]. Arthritis Rheum, 2010, 62(9): 2569-2581.
[2] Myasoedova E, Crowson CS, Kremers HM, et al. Is the incidence of rheumatoid arthritis rising: results from Olmsted County, Minnesota, 1955-2007 [J]. Arthritis Rheum, 2010, 62(6): 1576-1582.
[3] Smolen JS, Aletaha D, Mcinnes IB. Rheumatoid arthritis [J]. Lancet, 2016, 388(10055): 2023-2038.
[4] Liew PX, Kubes P. The Neutrophil's Role During Health and Disease [J]. Physiol Rev, 2019, 99(2): 1223-1248.
[5] Fresneda Alarcon M, Mclaren Z, Wright HL. Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O [J]. Front Immunol, 2021, 12: 649693.
[6] Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis [J]. Sci Transl Med, 2013, 5(178): 178ra40.
[7] Corsiero E, Pratesi F, Prediletto E, et al. NETosis as Source of Autoantigens in Rheumatoid Arthritis [J]. Front Immunol, 2016, 7: 485.
[8] Ribon M, Seninet S, Mussard J, et al. Neutrophil extracellular traps exert both pro- and anti-inflammatory actions in rheumatoid arthritis that are modulated by C1q and LL-37 [J]. J Autoimmun, 2019, 98: 122-131.
[9] Wu S, Peng W, Liang X, et al. Anti-citrullinated protein antibodies are associated with neutrophil extracellular trap formation in rheumatoid arthritis [J]. J Clin Lab Anal, 2021, 35(3): e23662.
[10] Guan H, Xie L, Ji Z, et al. Triptolide inhibits neutrophil extracellular trap formation [J]. Ann Transl Med, 2021, 9(17): 1384.
[11] Odobasic D, Kitching AR, Yang Y, et al. Neutrophil myeloperoxidase regulates T-cell-driven tissue inflammation in mice by inhibiting dendritic cell function [J]. Blood, 2013, 121(20): 4195-204.
[12] Parker H, Dragunow M, Hampton MB, et al. Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus [J]. J Leukoc Biol, 2012, 92(4): 841-849.
[13] Singh JA, Cameron C, Noorbaloochi S, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis [J]. Lancet, 2015, 386(9990): 258-265.
[14] Cascao R, Rosario HS, Souto-Carneiro MM, et al. Neutrophils in rheumatoid arthritis: More than simple final effectors [J]. Autoimmun Rev, 2010, 9(8):531-535.
[15] Wright HL, Moots RJ, Edwards SW. The multifactorial role of neutrophils in rheumatoid arthritis [J]. Nat Rev Rheumatol, 2014, 10(10): 593-601.
