Toll-Like Receptor 4-Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2019 Jan 16

PMID 30643526

Citations 5

Authors

Qiaomei Dai

Ji Li

Yu Yun

Jianwei Wang

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the effect of shikonin on (CIA) collagen-induced arthritis and its influence and mechanism on the balance between Th17 cells and Treg cells.

Methods: Three doses of shikonin were administered orally to mice before the onset of CIA, and celecoxib was used as positive control drug. The arthritis response was monitored visually by macroscopic scoring and hindpaw swelling. Histology of knee was used to assess the occurrence of cartilage destruction and bone erosion. Serum collagen type II (C II) antibody levels associated with CIA were assessed with ELISAs. RT-PCR and quantitative PCR were employed to determine the mRNA expression of cytokines and TLRs in the surface of DCs in the patella with adjacent synovium and spleen in CIA. The expression of cytokines and transcription factors in the peripheral immune organs was tested by Western blotting.

Results: Shikonin treatment suppressed the macroscopic score and incidence of arthritis. Swelling of hind paws, cartilage destruction, and serum anti-C II concentration were delayed with shikonin when compared to controls. Shikonin treatment suppressed the arthritis in a dose-dependent manner. Moreover, the expression of Th17 cytokines (IL-17A) was greatly inhibited both in the synovium and spleen in treated groups compared with those in control groups. The mRNA and protein levels of IL-10 and TGF-, however, were upregulated after shikonin treatment. The expression of Foxp3 in the synovium and spleen was upregulated, and the expression of ROR-t in the synovium and spleen was downregulated after shikonin treatment through RT-PCR, quantitative PCR, and Western blotting. The DCs in the spleen of shikonin-treated mice had lower expression of TLR4 and MyD88, and the expression of TLR2 and TLR9 in the spleen was not different between the two groups.

Conclusion: Shikonin has anti-inflammatory effects on CIA. Shikonin treatment can inhibit Th17 cytokines expression and induce Treg responses through inhibiting the activation of TLR4/MyD88 pathway.

Citing Articles

Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases.

Wang X, Sun B, Wang Y, Gao P, Song J, Chang W Front Immunol. 2024; 15:1333993.

PMID: 38352872 PMC: 10861655. DOI: 10.3389/fimmu.2024.1333993.

Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis.

Yao X, Wang Q, Chen C, Zeng P, Hou L, Zhou J Evid Based Complement Alternat Med. 2022; 2022:5105545.

PMID: 35096112 PMC: 8799337. DOI: 10.1155/2022/5105545.

Shikonin attenuates rheumatoid arthritis by targeting SOCS1/JAK/STAT signaling pathway of fibroblast like synoviocytes.

He L, Luan H, He J, Zhang M, Qin Q, Hu Y Chin Med. 2021; 16(1):96.

PMID: 34600581 PMC: 8487562. DOI: 10.1186/s13020-021-00510-6.

TlR2 and TlR4 are involved in the treatment of rheumatoid arthritis synovial fibroblasts with a medicated serum of asarinin through inhibition of T1/T17 cytokines.

Dai Q, Li Y, Wang M, Li Y, Li J Exp Ther Med. 2020; 19(4):3009-3016.

PMID: 32256787 PMC: 7086207. DOI: 10.3892/etm.2020.8557.

Corrigendum to "Toll-Like Receptor 4-Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression".

Dai Q, Li J, Yun Y, Wang J Evid Based Complement Alternat Med. 2019; 2019:2198708.

PMID: 30984272 PMC: 6431497. DOI: 10.1155/2019/2198708.

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