Chitosan oligosaccharides inhibit LPS-induced over-expression of IL-6 and TNF-α in RAW264.7 macrophage cells through blockade of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways

Chitosan oligomers show various biological activities. However, its molecular mechanisms remain unknown in LPS-stimulated macrophages. Here, we explored the inhibitive effects of chitosan oligomers on LPS-induced IL-6/TNF-alpha production in macrophages. The results indicated chitosan oligomers pretreatment effectively inhibited LPS-induced over-expression of both inflammatory cytokines. Signal transduction studies show chitosan oligomers may repress not only the phosphorylation of p38, ERK1/2, JNK, phosphatidylinositol 3-kinase (PI3K) and Akt, but also the activation of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1). Furthermore, both the activation of NF-kappa B/AP-1 and the subsequent IL-6/TNF-alpha over-expression in LPS-induced macrophages are inhibited by specific p38 inhibitor (SB203580), ERK1/2 inhibitor (PD98059), JNK inhibitor (SP600125) and PI3K inhibitor (LY294002). In conclusion, our investigation suggests chitosan oligomers inhibited the elevated expression of IL-6/TNF-alpha in LPS-induced macrophages, regulated by MAPKs and PI3K/Akt pathways dependent on NF-kappa B/AP-1 activation. (C) 2011 Elsevier Ltd. All rights reserved.