Attenuation of pro-inflammatory mediators in LPS-stimulated BV2 microglia by chitooligosaccharides via the MAPK signaling pathway

Chitooligosaccharides (COS), depolymerized products of chitosan, has received considerable attention as bioactive material due to their biocompatible, biodegradable, non-toxic and non-allergenic natures. In this study. COS of four different molecular weight ranges (<1,1-3,3-5 and 5-10 kDa) were investigated for their abilities to modulate inflammatory mediators in lipopolysaccharides (LPS)-stimulated BV2 microglia. At the concentration of 500 mu g/ml, COS attenuate the productions of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. Furthermore, the release and expression levels of inflammatory cytokines: including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) were also attenuated by COS. Notably, the inhibitory activity of COS depends significantly on its molecular weight, with lower molecular weight showed higher activity. In addition, the suppressive effects on the phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) by COS were confirmed. These results indicate that COS could be used as an inhibitor in regulating microglial inflammatory responses. Moreover. COS may assist therapeutic treatment of neurodegenerative diseases which accompanied with microglial activation. (C) 2011 Elsevier B.V. All rights reserved.