Prevention of dextran sulfate sodium-induced mouse colitis by the fungal protein Ling Zhi-8 via promoting the barrier function of intestinal epithelial cells

• Published in: Food & function 2021-03, Vol.12 (4), p.1639-1650
• Main Authors: Chen, Yu-Huan, Shin, Jenn-Yeu, Wei, Hsiu-Mei, Lin, Chi-Chien, Yu, Linda C H, Liao, Wei-Ting, Chen, Dz-Chi, Chu, Ching-Liang
• Format: Article
• Language: English
• Subjects: Colitis; Cytokines; Dextran; Dextran sulfate; Dextrans; Electrical junctions; Electrical resistivity; Epithelial cells; Fungi; Immune system; Immunomodulation; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Kinases; Mushrooms; Myosin; Myosin-light-chain kinase; NF-κB protein; Permeability; Pretreatment; Proteins; Sodium; Sulfates; Tight junctions; TLR2 protein; Toll-like receptors
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d0fo02604b

The fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in protecting intestinal epithelial cells (IECs) is unknown. In this study, we aim to investigate the functional effect of LZ-8 on IECs. LZ-8 effectively rescued the pro-inflammatory cytokine-induced loss of tight junctions (TJs) by enhancing transepithelial electrical resistance (TEER), reducing permeability, and maintaining the distribution of TJ proteins, in Caco-2 cells. Mechanistically, LZ-8 blocked the upregulation of myosin light chain kinase (MLCK) and NF-kB activation by TLR2-mediated suppression of cytokine signaling (SOCS)-1 expression. Furthermore, LZ-8 pre-treatment reduced the pathological scores of dextran sulfate sodium (DSS)-induced colitis in mice. These results indicated that LZ-8 protected the barrier function of IECs against inflammation. Thus, LZ-8 may potentially be a novel candidate for treating inflammatory bowel disease (IBD).