RESUMO
Chitosan (300â¯kDa) was degraded by cellulase to chitosans with molecular weights (MWs) of 156, 72, 7.1, and 3.3â¯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, 72â¯kDa) significantly inhibited NO production, whereas smaller chitosans (7.1 & 3.3â¯kDa, COS) increased NO production. The 156 and 72â¯kDa chitosans significantly inhibited TNF-α and IL-6 production, whereas the 7.1â¯kDa chitosan and COS significantly induced their production. The 156 and 72â¯kDa chitosans inhibited NF-κB activation and iNOS expression by binding to the CR3 (for 156â¯kDa chitosan), or CR3 and TLR4 receptor (for 72â¯kDa chitosan). The smaller chitosans (e.g. 7.1â¯kDa chitosan and COS) activated NF-κB and enhanced iNOS expression by binding to CD14, TLR4, and CR3 receptors to activate JNK signaling proteins.