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Toll-Like Receptor 4–Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression.
- Source :
- Evidence-based Complementary & Alternative Medicine (eCAM); 12/16/2018, p1-9, 9p, 2 Charts, 3 Graphs
- Publication Year :
- 2018
-
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-β, however, were upregulated after shikonin treatment. The expression of Foxp3 in the synovium and spleen was upregulated, and the expression of ROR-γt 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- DRUG therapy for arthritis
ANIMAL experimentation
ARTHRITIS
ARTICULAR cartilage
CARRIER proteins
CELL receptors
CELLULAR signal transduction
COLLAGEN
CYTOKINES
DOSE-effect relationship in pharmacology
ENZYME-linked immunosorbent assay
GENE expression
HISTOLOGICAL techniques
INTERLEUKINS
KNEE
MESSENGER RNA
MICE
NONSTEROIDAL anti-inflammatory agents
ORAL drug administration
PATELLA
POLYMERASE chain reaction
SPLEEN
SYNOVIAL membranes
T cells
TRANSCRIPTION factors
TRANSFORMING growth factors-beta
WESTERN immunoblotting
PHYTOCHEMICALS
PLANT extracts
CYCLOOXYGENASE 2
TOLL-like receptors
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 1741427X
- Database :
- Complementary Index
- Journal :
- Evidence-based Complementary & Alternative Medicine (eCAM)
- Publication Type :
- Academic Journal
- Accession number :
- 133577430
- Full Text :
- https://doi.org/10.1155/2018/2428546