P115 Trehalose modulates Dextran Sulfate Sodium-induced colitis by regulating macrophage polarization
Li, Y.(1)*;Law, H.K.W.(1);
(1)Faculty of Health and Social Science- The Hong Kong Polytechnic University, Department of Health Technology and Informatics, Hong Kong, Hong Kong- China;
Background
Inflammatory bowel disease (IBD) is a collective term for chronic inflammatory diseases resulting from complex genetic susceptibility, microbial flora, and immune abnormality. Due to the complicated pathogenesis, therapies for IBD are largely limited to the treatment of symptoms. However, these existing drugs sometimes fail or lead to adverse effects in long-term therapies. The development of new drugs and new therapies for IBD are still the top priorities. Trehalose (TRE) is an autophagy inducer through an mTOR-independent pathway. Given its safe and protective nature, TRE has gained significant attention for the potential application in disease treatment. It is a natural product that may be used as a harmless autophagy regulator. In our research, we use the Dextran Sulfate Sodium (DSS)-induced IBD model to explore the therapeutic effects of trehalose on autophagy and inflammation in mice.
Methods
6-8 weeks old C57BL/6J male mice were used for experiments. Mice were given 2% DSS (MP Biomedicals) in autoclaved drinking water for 4 days to induce colitis, Then TRE (2 g/kg body weight, Sigma-Aldrich), rapamycin (1.25 mg/kg body weight, MedChemExpress) or normal saline were intraperitoneally injected for 5 days. Mice were weighed daily, and stool consistency, diarrhea, or blood in the stools were monitored to calculate the disease activity index (DAI). At the end of the experiment, the colons were measured, opened longitudinally, and handled according to standard procedures. The tissue samples were collected for RNA, protein extraction, histology, and macrophage isolation respectively. Western Blot was used for autophagy analysis and flow cytometry was used for macrophage subtype and apoptosis analysis. Besides, Real-time quantitative PCR assay was used for examining the cytokine expression.
Results
In TRE-treated mice, the cessation of diarrhea and anal bleeding occurred earlier and hence the DAI scores decreased more rapidly when compared to the other groups. Correspondingly, the colons in TRE-treated mice shortened less than the saline treated control suggesting recovery from DSS-induced colitis. Even though no significant difference was observed in H&E staining and tissue scores for mice in different groups, significant difference in macrophage polarization and cytokine production was observed. DSS-induced intestinal CD86+ macrophages, whereas TRE treatment increased CD206+ macrophages and decreased the expression of pro-inflammatory cytokines, such as IL-6 and TNF-alpha.
Conclusion
Our results demonstrate that TRE decreases the symptoms of experimental colitis by regulating macrophage polarization, probably mediated by macrophage autophagy. These findings indicate the potential of TRE to be an adjuvant therapy for IBD.