Abstract
Context
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of gastrointestinal tract, which can develop into colorectal cancer. Triptolide (TP) is a predominant bioactive ingredient of Tripterygium wilfordii Hook.F., and has been proven to have the therapeutic potential for various human diseases.
Objective
In our study, we examined the function of TP in the progression of IBD.
Methods
3-(4,5)dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay was used to evaluate the viability of RAW264.7 cells. Quantitative reverse transcription polymerase chain reaction assay was performed to detect the relative gene expression. Western blot was used to detect the relative protein expression. Enzyme-linked immunosorbent assay was utilized to examine the levels of prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-6.
Result
Our research demonstrated that TP restrained lipopolysaccharide (LPS)-caused activation of RAW264.7 cells, as evidenced by the reduction of PGE2, TNF-α, and IL-6, and increase of IL-10. TP treatment also restrained M1-type macrophage polarization and facilitated M2-type macrophage polarization of RAW 264.7 cells in the presence of LPS. Moreover, TP mitigated LPS-induced activation of the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling in RAW264.7 cells. Further, activation of the mTOR/STAT3 signaling by MHY1485 attenuated the effect of TP in regulation of macrophage polarization in RAW264.7 cells in the presence of LPS.
Conclusion
Overall, our results indicated that TP attenuated LPS-induced activation of RAW 264.7 macrophages by inducing M1-to-M2 repolarization via repression of the mTOR/STAT3 signaling. Therefore, TP might be an effective agent for IBD treatment.
Acknowledgement
Not applicable.
Author contributions
Huanhuan Zhu and Chunwei Li made majority contribution to the conception of this study, Shaopeng Tong and Congrong Yan carried out all of experiments, Acheng Zhou and Minying Wang prepared the first draft of this manuscript. Chunwei Li agreed the final design of this work and revised this manuscript critically. Huanhuan Zhu performed cell culture and Western blot. All authors have read and approved the final manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.