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.

• Authors: Yosuke Nishitani, Ling Zhang, Masaru Yoshida, Takeshi Azuma, Kazuki Kanazawa, Takashi Hashimoto, Masashi Mizuno
• Journal: PloS one (PLoS One) Vol. 8 Issue 4 Pg. e62441 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23630633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Interleukin-8
• Lipopolysaccharides
• RELA protein, human
• RNA, Messenger
• Receptors, Tumor Necrosis Factor, Type I
• Transcription Factor RelA
• Cytochalasin D
• Lentinan

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Caco-2 Cells
• Cell Nucleus (metabolism)
• Coculture Techniques
• Colitis (drug therapy, immunology, metabolism)
• Colon (drug effects, metabolism, pathology)
• Cytochalasin D (pharmacology)
• Cytokines (genetics, metabolism)
• Endocytosis (drug effects)
• Epithelial Cells (drug effects, immunology, metabolism)
• Gene Expression (drug effects)
• Humans
• Interleukin-8 (genetics, metabolism)
• Intestinal Mucosa (drug effects, immunology, metabolism)
• Lentinan (pharmacology, therapeutic use)
• Lipopolysaccharides (pharmacology)
• Mice
• Protein Transport
• RNA, Messenger (genetics, metabolism)
• Receptors, Tumor Necrosis Factor, Type I (genetics, metabolism)
• Transcription Factor RelA (metabolism)