Triptolide alleviates collagen-induced arthritis in mice by modulating Treg/Th17 imbalance through the JAK/PTEN-STAT3
Yao Huang1, Xin Ba1, Hui Wang2
1Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background:
This study aimed to investigate the effects of triptolide (TP) on collagen-induced arthritis (CIA) mice and the related mechanisms.
Methods:
CIA mice were administered TP for 35 days. Mouse ankle joints and serum antibodies and cytokines were examined to assess the therapeutic effects of TP. The ratios of Treg, Th1 and Th17 cells were measured by flow cytometry and RT-qPCR. Reverse docking was used to characterize the binding modes of TP against target proteins. The expression of the STAT3 pathway in CIA mice was evaluated by western blotting and immunofluorescence staining. Mouse spleen lymphocytes were extracted, and the expression of the STAT3 pathway after IL-6 stimulation was analysed.
Results:
TP could significantly alleviate joint swelling, reduce bone destruction and downregulate serum inflammation levels. TP improved the imbalance of Treg/Th17 cells in CIA mice. TP could form stable complexes with target proteins. TP significantly inhibited the activation of the JAK/PTEN-STAT3 pathway in mice. Moreover, TP regulated the activation of the JAK1/2-STAT3 signalling pathway in mouse spleen lymphocytes under inflammatory stimulation.
Conclusion:
TP can inhibit inflammation and alleviate bone destruction in CIA mice. The underlying mechanism is related to the regulation of the imbalance of Treg/Th17 cells through the JAK/PTEN-STAT3 pathway.
Insights
Triptolide (TP) effectively reduces inflammation and bone damage in collagen-induced arthritis (CIA) mice by regulating T cell balance and inhibiting the JAK/PTEN-STAT3 pathway.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Background:
- Collagen-induced arthritis (CIA) is a mouse model for rheumatoid arthritis.
- Investigating novel therapeutic agents for CIA is crucial.
Purpose of the Study:
- To evaluate the therapeutic effects of triptolide (TP) in CIA mice.
- To elucidate the underlying mechanisms of TP's action.
Main Methods:
- CIA mice were treated with TP for 35 days.
- Assessed joint swelling, bone destruction, serum markers, and immune cell populations (Treg, Th1, Th17).
- Utilized molecular techniques including flow cytometry, RT-qPCR, western blotting, immunofluorescence, and reverse docking to analyze the JAK/PTEN-STAT3 pathway.
Main Results:
- TP significantly reduced joint swelling, bone destruction, and systemic inflammation.
- TP treatment corrected the Treg/Th17 cell imbalance in CIA mice.
- TP inhibited the JAK/PTEN-STAT3 signaling pathway activation in vivo and in vitro.
Conclusions:
- Triptolide demonstrates significant anti-inflammatory and bone-protective effects in CIA mice.
- TP's mechanism involves modulating Treg/Th17 cell balance via the JAK/PTEN-STAT3 pathway.
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