Table 1.

Different pathways for inhibiting NET formation.

Category	Mechanisms regulating NETs	Reference
Immunomodulatory	CsA by downregulating NFAT and inhibiting the calcineurin pathway and then regulating NETs formation. Rapamycin inhibits fMLP-driven NETs formation by disrupting autophagosome formation.	[105] [107]
Anti-platelet	APC can reduce platelet adhesion to NETs by cleaving and detoxifying extracellular histones. Thrombomodulin limits the procoagulant response and inhibits LPS-induced NETosis. Anti-HMGB1 antibody reduces NETs formation by decreasing the interaction between TLR4 and HMGB1.	[108] [109] [110]
Anti-Inflammatory	PGE2 can activate the CAMP-PKA pathway and inhibit PMA-induced NETs formation. Aspirin inhibits NF-κB and regulates NETs formation. Antibiotics affect neutrophil activation and migration and play a role in regulating NETs.	[111] [112] [113,114]
Regulatory factors	AntagomiR-155 can reduce the levels of PAD4 and DNA histone complexes in PMN-stimulated neutrophils, and then regulate the generation of NETs. Cl-amidine as an inhibitor of PAD4, reduced NET-neutrophils. PA-dPEG24 can inhibit the activity of myeloperoxidase and reduce neutrophil NETs production. DPI inhibits the formation of NETs by inhibiting the production of NADPH oxidase and ROS. NAC regulates the production of ROS and affects the generation of NETs.	[115] [116] [117,118] [119,120] [121,122]
Nucleases	DNase degrades NETs by destroying their backbone. Staphylococcus aureus degrades NETs by converting NETs to deoxyadenosine.	[123] [124]
Cell cycle	Negative regulation of cell cycle regulators blocks cell cycle proteins and inhibits NETs production. Abemaciclib inhibition interrupts the cell cycle process and thus inhibits NETs release.	[26] [125]