Insights into the pathogenic roles and targeted therapy of neutrophil extracellular traps in inflammatory bowel disease

Figure 3 Neutrophil extracellular traps constitute a central component in thrombosis formation and colitis-associated colorectal cancer. Neutrophil extracellular traps promote the thrombotic tendency in inflammatory bowel disease. The molecular mechanisms included in colitis-associated colorectal cancer: Mutations on protein p53 result in its over-expression and the turbulence of anti-tumor signaling. MyD88-dependent Toll-like receptor 4 alterations trigger and amplify a pro-inflammatory environment through nuclear factor kappa-B pathway. Cyclooxygenase-2 up-regulates prostaglandin E2 production, which in turn promotes angiogenesis and modulates immune responses through phosphatidylinositol 3-kinase (PI3K) signaling. The PI3K/protein kinase B axis stimulates many cytokines and facilitates glucose transporter 4 migration, thereby enhancing metabolic activity in T helper (Th) 2 and Th17 lymphocytes. TF: Tissue factor; NETs: Neutrophil extracellular traps; IBD: Inflammatory bowel disease; CAC: Colitis-associated colorectal cancer; TLR: Toll-like receptor; PGE2: Prostaglandin E2; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; NF-κB: Nuclear factor kappa-B; COX-2: Cyclooxygenase-2.