Effect of chitosan molecular weight on anti-inflammatory activity in the RAW 264.7 macrophage model

Chitosan (300 kDa) was degraded by cellulase to chitosans with molecular weights (MWs) of 156, 72, 7.1, and 3.3 kDa and a chitooligosaccharide mixture (COS). Effects of these on NO secretion, cytokine production, and mitogen-activated protein kinase pathways in lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages were investigated. Larger chitosans (300, 156, 72 kDa) significantly inhibited NO production, whereas smaller chitosans (7.1 & 3.3 kDa, COS) increased NO production. The 156 and 72 kDa chitosans significantly inhibited TNF-α and IL-6 production, whereas the 7.1 kDa chitosan and COS significantly induced their production. The 156 and 72 kDa chitosans inhibited NF-κB activation and iNOS expression by binding to the CR3 (for 156 kDa chitosan), or CR3 and TLR4 receptor (for 72 kDa chitosan). The smaller chitosans (e.g. 7.1 kDa chitosan and COS) activated NF-κB and enhanced iNOS expression by binding to CD14, TLR4, and CR3 receptors to activate JNK signaling proteins.