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Leonurine Regulates Treg/Th17 Balance to Attenuate Rheumatoid Arthritis Through Inhibition of TAZ Expression
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 11 (2020)
- Publication Year :
- 2020
-
Abstract
- Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4+ T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naive CD4+ T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1β, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1β, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.
- Subjects :
- 0301 basic medicine
lcsh:Immunologic diseases. Allergy
CD4-Positive T-Lymphocytes
Treg Th17
rheumatoid arthritis
TAZ
medicine.medical_treatment
Immunology
T-Lymphocytes, Regulatory
Immunophenotyping
Arthritis, Rheumatoid
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Gallic Acid
medicine
Immunology and Allergy
Humans
Receptor
Original Research
biology
Activator (genetics)
Cell growth
Gene Expression Profiling
Interleukin
balance
Leonurine
Immunohistochemistry
030104 developmental biology
Cytokine
chemistry
Gene Expression Regulation
RANKL
leonurine
biology.protein
Cancer research
Th17 Cells
Tumor necrosis factor alpha
lcsh:RC581-607
Acyltransferases
Biomarkers
030215 immunology
Transcription Factors
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in immunology
- Accession number :
- edsair.doi.dedup.....8eb7070ac49344245fcab8548ea4fb3c