P031 Class A1 scavenger receptor mediates macrophage polarization and apoptotic progression in a murine dextran sulfate sodium-induced colitis
Su, J.(1);Xie, C.(1);Hu, Y.(1);Huang, Q.(1);Shi, H.(1);Wang, L.(1);Ren, J.(1);
(1)Affliated Zhongshan Hospital of Xiamen University, Department of Gastroenterology, Xiamen- Fujian Province, China
This study aimed to investigate the role of class A1 scavenger receptor (SR-A1) for regulating macrophage function and apoptotic pathway during intestinal inflammation of inflammatory bowel disease (IBD) in a DSS-induced murine colitis model.
A murine colitis model was established by feeding with 5% dextran sulfate sodium (DSS). Treatment groups were injected intravenously with SR-A1 antibody (100ug/kg), and control groups were injected with the vehicle only. Inflammatory activity and histological changes were evaluated on Day 8, and the percentage of macrophage markers in lamina propria mononuclear cells (LPMC) was measured by flow cytometer. The apoptosis and proliferation of intestinal epithelial cells were detected by TUNEL and Ki67 staining, and the expressions of related signaling pathway protein were determined with western blot.
Treatment group showed a preventive effect on colitis symptoms and fewer inflammatory cell infiltrates compared with control group. After SR-A1 antibody treatment, flow cytometry of LPMC indicated that the percentage of F4/80+CD206+ Macrophages was elevated, while the percentage of F4/80+CD11c+ Macrophages was not obviously changed. Immunohistochemistry revealed that TUNEL-positive cells were significantly downregulated and Ki67- positive cells were upregulated in colonic mucosa of treatment group. In addition, the expressions of TLR4, MyD88 and NF-kB proteins in colonic mucosa were decreased after SR-A1 antibody injection.
Treatment with SR-A1 antibody could ameliorate macrophage-associated inflammatory response and epithelial cell apoptosis in a murine colitis model, which suggested that SR-A1 was a negative regulator of M2 polarization in IBD. SR-A1 mediated its effect by synergizing with TLR4/ MyD88 / NF-kB signaling pathway. Our research identified SR-A1 as a potential therapeutic target in IBD.