Fig. 3: Ferroptosis and SAP-associated inflammatory cells. | Cell Death Discovery

Fig. 3: Ferroptosis and SAP-associated inflammatory cells.

From: Ferroptosis exacerbates hyperlipidemic acute pancreatitis by enhancing lipid peroxidation and modulating the immune microenvironment

Fig. 3

DAMPs released after ferroptosis bind to TLR4 to increase the production of NETs to exacerbate pancreatic injury. Macrophages use TLR2 to recognize oxidized phospholipids and then phagocytose ferroptotic cells and progressively release HMGB-1, which promotes M1 macrophage polarization to enhance inflammatory responses. GPX4 downregulation promotes immune responses in Th1 and Th17 cells to increase the severity of inflammation. In contrast, low METTL3 expression increases GPX4 expression, which subsequently reduces NET formation by inhibiting ferroptosis. RSL3 alleviates the AP-associated inflammatory response by reducing M1 macrophage polarization through the inhibition of iNOS expression. GPX4 upregulation inhibits the proinflammatory effects of Th1 and Th17 cells (DAMP, damage-associated molecular pattern; TLR4, Toll-like receptor 4; TLR9, Toll-like receptor 9; NETs, neutrophil extracellular traps; HMGB-1, high mobility group box-1; TLR2, Toll-like receptor 2; GPX4, glutathione peroxidase 4; iNOS, inducible nitric oxide synthase; METTL3, methyltransferase-like 3; RSL3, an inhibitor of GPX4).

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