OH-CATH30 targets CD40 to suppress NF-κB signaling and promote arachidonic acid metabolic reprogramming in acute pancreatitis

Figure 8 Schematic model of OH-CATH30 ameliorating acute pancreatitis by targeting CD40. OH-CATH30 binds to CD40, which suppresses the downstream CD40-tumor necrosis factor receptor-associated factor 6-transforming growth factor beta-activated kinase 1-nuclear factor-kappa B signaling cascade in cerulein-induced acute pancreatitis mice model. This inhibition reduces pro-inflammatory cytokine production, drives M1-to-M2 macrophage phenotypic shift, and downregulates cyclooxygenase-2/5-lipoxygenase to inhibit arachidonic acid metabolism and synthesis of pro-inflammatory lipid mediators. These synergistic effects attenuate pancreatic and systemic inflammation, alleviate pancreatic injury, and ameliorate acute pancreatitis pathogenesis. IL: Interleukin; TNF-α: Tumor necrosis factor-α; NF-κB: Nuclear factor-kappa B.