Triptolide attenuates LPS-induced activation of RAW 264.7 macrophages by inducing M1-to-M2 repolarization via the...

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.

In our study, we examined the function of TP in the progression of IBD.

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.

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.

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.