Chitooligosaccharides Attenuate Lipopolysaccharideinduced Inflammation and Apoptosis of Intestinal Epithelial Cells: Possible Involvement of TLR4/NF-κB Pathway.

Abstract

Marine-derived chitooligosaccharides (CHOS) are a new class of anti-inflammatory natural products characterized by its nontoxity, low-cost and small-molecule. But whether CHOS exert a protective action against inflammatory bowel diseases (IBDs) is not yet fully understood. This paper studied the effect of CHOS on the inflammation and apoptosis of intestinal epithelial cells (IECs) using lipopolysaccharides (LPS)-stimulated Caco-2 cells as an in vitro model of IBD. Caco-2 cells were pre-incubated with various concentrations of CHOS (0.25, 0.5 and 1.0 mg/ml) for 2 h prior to being co-stimulated or not with LPS at a concentration of 1µg/mL for 48h. Cell apoptosis was measured with Annexin V-FITC and propidium iodide (PI) assay by flow cytometry. The levels of proinflammatory mediators including tumor necrosis factor (TNF)-α, interleukin-8 and prostaglandin (PG) E2 were analyzed using Enzyme-linked Immunosorbent Assay. And the cell expression of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), caspase-3, bcl-2, and cyclooxygenase (COX)-2 was examined by western blot. We observed that CHOS significantly and concentration-dependently inhibited the LPS-induced inflammatory response and apoptosis of IECs, which was evidenced by the reduction in the release of proinflammatory mediators TNF-α, PGE2, the expression of COX-2, apoptotic (Annexin V + /PI -) cell populations, the pro-apoptotic caspase-3 expression, and the enhancement of the expression level of anti-apoptotic bcl-2. And CHOS treatment significantly reduced the protein expressions of TLR4 and NF-κB in LPS-stimulated Caco-2 cells. Thus, the present study suggests the potential medical use of CHOS in the control of IBDs, which may be due to the downregulation of TLR4/NF-κB pathway.

Chitosan and chitooligosaccharides attenuate soyabean meal-induced intestinal inflammation of turbot (Scophthalmus maximus): possible involvement of NF-кB, activator protein-1 and mitogen-activated protein kinases pathways

“…In this study, Compelling investigations in humans and other higher organisms have shown that the secretion of pro-inflammatory cytokines can play an essential role in the progression of inflammatory bowel disease (53) . It has been indicated that both CTS and COS supplementation can attenuate intestinal inflammation by suppressing the expression of certain cytokines as well as the production of inflammatory regulators both in vivo (54)(55)(56) and in vitro (57,58) . Hence, according to our present study, it is reasonable that CTS or COS supplementation in fish diet can attenuate SBM-induced inflammatory response in turbot, partially by suppressing the production of pro-inflammatory cytokines.…”

The potentiality of using chitosan and its enzymatic depolymerized derivative chito-oligosaccharides as immunomodulators

“…Natural products had received much attention to modulate the immune system since the current treatments induce severe side effects (Mei et al, 2013;Yang et al, 2016). Several natural compounds as polysaccharides and oligosaccharides reported to enhance the immune system (Petrovsky et al, 2011).…”

“…Lipopolysaccharide (LPS) is the glycolipid constituent of the outer membrane of all pathogenic gram-negative bacteria that known as one of the most potent activators of the inflammatory responses. LPS activates the inflammatory signal transduction by the cell surface toll-like receptor-4 (TLR-4) that results in cellular activation and pro-inflammatory gene expression (Yang et al, 2016).…”

Chitin and Chitosan Derivatives as Biomaterial Resources for Biological and Biomedical Applications

“…Likewise, it was shown that an oral intake of chitosan oligosaccharide (20 mg/kg/day) alleviated DDS-induced acute and chronic colitis in mice by inhibiting an NF-κB pathway [ 165 ]. Moreover, chitosan oligosaccharide downregulated NF-κB downstream targets such as COX-2 and upstream targets such as TLR-4 in lipopolysaccharide-induced inflammation in intestinal epithelial cells [ 166 ]. Furthermore, 50-200 µg/mL of a highly N -acetylated chitosan oligosaccharide inhibited protein expression of PI3K/Akt signaling pathway, which was involved in proinflammatory cytokine production in RAW 264.7 macrophage cells [ 167 ].…”