Published online Dec 7, 2019. doi: 10.3748/wjg.v25.i45.6634
Peer-review started: August 9, 2019
First decision: September 19, 2019
Revised: October 3, 2019
Accepted: November 13, 2019
Article in press: November 13, 2019
Published online: December 7, 2019
Inflammatory bowel disease (IBD) is characterized by chronic and non-specific inflammation of the intestinal mucosa and mainly includes ulcerative colitis and Crohn's disease. The incidence of IBD is increasing, and the disease has gained growing attention due to its substantial impacts on patient quality of life and increased side effects of traditional drugs in the treatment of IBD, so it is important to find new methods to treat IBD.
Toxoplasma ROP16I/III(ToxoROP16I/III) induced RAW264.7 polarization to M2 macrophage, down-regulated the M1-associated inflammation response and played a protective role in Caco-2 intestinal epithelial cells.
The pathogenesis of IBDs remains unclear and the efficacy of current treatments is uncertain. Toxoplasma ROP16I/III-induced M2 macrophages might provide a promising strategy for the immunotherapy of IBDs using the parasite-derived molecules.
ToxoROP16I/III induced RAW264.7 polarization to M2 macrophage, enhanced the synthesis of arginase-1 (Arg-1), interleukin (IL)-10, transformed growth factor (TGF)-β1, and IL-13, down-regulated the M1-associated inflammation response IL-1β, tumor necrosis factor (TNF)-α, IL-6, nitric oxide (NO), and inducible nitric oxide synthase (iNOS) as shown by quantitative real-time reverse transcriptase polymerase chain reaction. M1 and M2 cells co-cultured with Caco-2 cells through transwell alleviated Caco-2 cell apoptosis and its associated proteins by flow cytometry assay and Western blotting.
M1 cells exhibited dramatically increased production of iNOS, NO, TNF-α, IL-1β, and IL-6, while ToxoROP16I/III induced macrophage bias to M2 cells in vitro, showing increased expression of Arg-1, IL-10, and TGF-β1 and elevated production of p-Stat3 and p-Stat6. The M2 mixed with M1 cell culture downregulated the production of iNOS, NO, TNF-α, IL-1β, and IL-6 by M1 cells, resulting in apoptotic alleviation of Caco-2 cells.
ToxoROP16I/III-induced macrophages with an M2 phenotype inhibited the apoptosis of Caco-2 cells caused by lipopolysaccharide macrophage stimulation. These findings may be helpful for gaining a better understanding of the underlying mechanism and may represent a promising strategy for a novel immunotherapy against IBD.
ToxoROP16I/III may be a new method for the treatment of IBD, and there are few side effects in the course of treatment. It will become another new aspect of study in the treatment of IBD.