Chitosan oligosaccharides suppressant LPS binding to TLR4/MD-2 receptor complex

Lipopolysaccharide, a potent activator of the immune system, elicits the production of pro-inflammatory mediators in immunocytes. Toll-like receptor 4 (TLR4) and myeloid differentiation factor (MD) 2 receptor complex is required for recognition and signaling of LPS. Previous study suggested water soluble chitosan decreased secretion of pro-inflammatory cytokines TNF-alpha and IL-6. However, no studies have provided direct target and molecular mechanism of anti-inflammatory effect of chitosan oligosaccharide on LPS-stimulated cells. In this study, we found that chitosan oligosaccharides significantly inhibited binding of LPS to TLR4/MD-2 receptor complex, thus attenuated activation of mitogen-activated protein kinases (MAPKs) and decreased nuclear translocation of nuclear factor-kappa B (NF-kappa B). Finally, chitosan oligosaccharides reduced the production of pro-inflammatory mediator, such as IL-1 beta and nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Therefore, chitosan oligosaccharides are potential inhibitive effector of LPS. (C) 2010 Elsevier Ltd. All rights reserved.