Targeted suppression of Act1 in the macrophages ameliorates experimental ulcerative colitis in mice induced by dextran sodium sulfate / 中国实验动物学报

ABSTRACT

Objective To investigate the role of macrophage?derived Act1 (nuclear factor kappa B activator 1) in the inflammatory bowel disease. Methods Genetically engineered mice carrying targeted suppression of Act1 in the mac?rophages (Anti?Act1) were used for the dextran sodium sulfate (DSS)?induced ulcerative colitis. The severity of colitis was assessed by weight loss, stool consistency, fecal blood index, colorectal length and H&E histology. The infiltration of CD45 + leukocytes and CD68 + macrophages in the inflammatory intestine was observed by immunohistochemical staining and expression levels of mRNA for inflammatory cytokines in colon tissues were analyzed by RT?qPCR. Results As com?pared with C57 mice, the anti?Act1 mice exhibited less severe acute colitis following DSS treatment, with reduced CD45 +leukocyte and CD68 + macrophage infiltrates in the colon tissue. Inflamed colons of the anti?Act1 mice expressed lower mR?NA levels of TNF?α, IL?1βand IL?6. Conclusions Targeted suppression of Act1 in the macrophages ameliorates dextran sodium sulfate?induced intestinal inflammation.