Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. It is unknown whether β-1,3;1,6-glucan can induce immune suppressive effects. Here, we study intestinal anti-inflammatory activity of Lentinula edodes-derived β-1,3;1,6-glucan, which is known as lentinan. Dextran sulfate sodium (DSS)-induced colitis mice were used to elucidate effects of lentinan in vivo. In the cellular level assessment, lentinan was added into a co-culture model consisting of intestinal epithelial Caco-2 cells and LPS-stimulated macrophage RAW264.7 cells. Ligated intestinal loop assay was performed for assessing effects of lentinan on intestinal epithelial cells (IECs) in vivo. Oral administration of lentinan (100 µg/mouse) significantly ameliorated DSS-induced colitis in body weight loss, shortening of colon lengths, histological score, and inflammatory cytokine mRNA expression in inflamed tissues. Lentinan reduced interleukin (IL)-8 mRNA expression and nuclear factor (NF)-κB activation in Caco-2 cells without decreasing of tumor necrosis factor (TNF)-α production from RAW264.7 cells. Flow cytometric analysis revealed that surface levels of TNF receptor (TNFR) 1 were decreased by lentinan treatment. A clathrin-mediated endocytosis inhibitor, monodansylcadaverine, canceled lentinan inhibition of IL-8 mRNA expression. Moreover, lentinan inhibited TNFR1 expression in Caco-2 cells in both protein and mRNA level. Lentinan also inhibited TNFR1 mRNA expression in mouse IECs. These results suggest that lentinan exhibits intestinal anti-inflammatory activity through inhibition of IL-8 mRNA expression associated with the inhibition of NF-κB activation which is triggered by TNFR1 endocytosis and lowering of their expression in IECs. Lentinan may be effective for the treatment of gut inflammation including IBD.
Highlights
The gastrointestinal tract of higher organisms is lined with a single layer of intestinal epithelial cells (IECs)
Mouse Characteristics To study the effect of lentinan on the innate immune response during colonic inflammation, an innate immune-mediated model of colitis induced by Dextran sulfate sodium (DSS) was performed
The colon length of DSStreated mice with lentinan at the concentration of 100 mg/mouse (5.9860.32 cm) was significantly longer than DSS-treated mice (4.8760.22 cm) (Fig. 1B and 1C). These results suggest that oral administration of lentinan has inhibitory activity on body weight loss and shortening of the colon in DSS-induced colitis
Summary
The gastrointestinal tract of higher organisms is lined with a single layer of IECs. This physical barrier separates subepithelial mucosal immune cells such as lymphocytes, macrophages, and dendritic cells from a variety of antigenic substances present within the intestinal lumen including bacteria and food antigens [1,2]. The clinical features of ulcerative colitis include severe diarrhea, blood loss, and progressive loss of peristaltic function [4]. While their precise etiology still remains unknown, understanding of the pathophysiology of IBD has advanced, and the typical features of these diseases have been shown in various studies, especially for intestinal immune cells and IECs of IBD patients. Lamina propria mononuclear cells (LPMCs) from patients with Crohn’s disease spontaneously secreted TNF-a [8] It is well-known that the secretion of inflammatory cytokines like IL-8 and TNF-a may be an important part of the immune response, and the dysregulation of these cytokines is implicated in the pathogenesis of IBD [9,10]
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