Intestinal Anti-Inflammatory Activity of Lentinan: Influence on IL-8 and TNFR1 Expression in Intestinal Epithelial Cells

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.

Lentinula edodes Genome Survey and Postharvest Transcriptome Analysis

“…Lentinula edodes is used as a medicinal mushroom; lentinan, a ␤-1,3-1,6-glucan with antitumor activity, is present in this mushroom (3). Recently, it was shown that lentinan can be effective for treating gut inflammation (4). It is also reported that polysaccharides extracted from Lentinula edodes can restore age-attenuated immune responses and reverse age-related alterations of gut microbiota compositions in mice (5).…”

Epigallocatechin-3-Gallate Regulates Anti-Inflammatory Action Through 67-kDa Laminin Receptor-Mediated Tollip Signaling Induction in Lipopolysaccharide-Stimulated Human Intestinal Epithelial Cells

“…IBD is characterized by the destruction of gut tissue, which is initiated from alterations of the intestinal epithelium barrier function involving increased tight junction permeability and maintained by a defective down-regulation of mucosal immunity toward the intestinal microflora [2]. Importantly, this disease is mediated by proinflammatory cytokines and inflammatory mediators [1, 3-5]. Among them, nitric oxide (NO) is a potential biomarker of disease activity in IBD.…”

“…Additionally, intestinal inflammation is also deeply mediated to the production of inflammatory cytokines such as tumor necrosis factor (TNF)- α, interleukin (IL)-6 and IL-1β [4]. Previous research reported that cytokines, especially IL-8, play a crucial role in the pathogenesis of IBDs, such as Crohn’s disease and ulcerative colitis, where they control multiple aspects of the inflammatory response [5]. Thus, understanding the regulating mechanisms of the factors involved in IBD pathogenesis will be important for the effective control of intestinal inflammation.…”

Lentinus edodesSuppresses Allergen-Induced Airway Hyperresponsiveness and Inflammation by Downregulating Nuclear Factor-kappa B Activity in a Murine Model of Allergic Asthma

“…In addition, several researchers have revealed that lentinan, β-glucan from Lentinus edodes, induces immunomodulatory and immunosuppressive behaviors under different conditions through MAPK signaling pathways mediated by ERK1/2 and JNK1 /2 [3,5]. Furthermore, the recent study provides evidence that lentinan could inhibit gut inflammation via modulation of NF-κB activity in the experimental models [34]. In view of these findings and our results, the polysaccharides isolated from Lentinus edodes might be active components attributed to the anti-asthmatic activity of LE.…”