Class A1 scavenger receptors mediated macrophages in impaired intestinal barrier of inflammatory bowel disease

Chenxi Xie, Yanyun Fan, Yinshi Huang, Shuangting Wu, Haimei Xu, Lupeng Liu, Yiqun Hu, Qingwen Huang, Huaxiu Shi, Lin Wang, Hongzhi Xu, Jingling Su, Jianlin Ren


Background: This study was to investigate the cytokines and phenotype of macrophages pre-treated with class A1 scavenger receptor (SR-A1) antibody in vitro and the influence on apoptotic pathway of colonic epithelial cells, and to explore the role of SR-A1 mediated macrophages in impaired intestinal barrier of inflammatory bowel diseases (IBDs).
Methods: Mouse macrophage RAW264.7 was pre-treated with SR-A1 antibody in the presence of lipopolysaccharide (LPS). Transwell system was employed for co-culture of RAW264.7 and Caco-2 in the presence of LPS and IFN-γ, with or without SR-A1 antibody pre-treatment. The percentage of F4/80+CD11c+ macrophages, apoptosis rate of Caco-2 cells, and expression of apoptosis and tight junction proteins in Caco-2 cells was determined.
Results: Pre-treatment with SR-A1 antibody up-regulated IL-10 expression in RAW264.7, whereas down- regulated the expression of TNF and iNOS. Immunofluorescence staining indicated the upregulation of NF-κB p-p56 after LPS stimulation was significantly inhibited in the presence of SR-A1 antibody. The increase in p-JNK expression was inhibited by SR-A1 antibody. Transwell assay showed the percentage of F4/80+CD11c+ macrophages and apoptotic Caco-2 cells increased after treatment with LPS and IFN-γ, which could be reversed in the presence of SR-A1 antibody. The induction of cleaved caspase-3 and claudin-1 in Caco-2 cells was also suppressed when SR-A1 antibody pre-treatment.
Conclusions: Pre-treatment with SR-A1 antibody can inhibit inflammatory response in LPS-induced macrophages in a NF-κB dependent manner. Pre-treatment with SR-A1 antibody also inhibits M1 phenotype expression of macrophages, and attenuates the pro-apoptotic effect on colonic epithelial cells and disruption of intestinal barrier integrity induced by macrophages.