Apurinic/apyrimidinic endonuclease 1/reduction-oxidation effector factor-1 (APE1) regulates the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome through modulating transcription factor NF-κB and promoting the secretion of inflammatory mediators in macrophages.

摘要: Background Inflammatory mediators play an important role in the occurrence, development, and metastasis of tumors. The aim present study was to elucidate effect apurinic/apyrimidinic endonuclease 1/reduction-oxidation effector factor-1 (APE1) on inflammatory mediator secretion, which is dependent APE1-mediated NLR family pyrin domain containing 3 (NLRP3) regulatory mechanism. Methods human myeloid leukemia mononuclear cell line (THP-1) cells were cultured polarized M2 subset macrophages. Enzyme-linked immunosorbent assay used for determining tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-18, IL-10, IL-33 levels. Reverse transcription-polymerase chain reaction western blot evaluating TNF-α, 1 (NLRP1), NLRP3, caspase-1, apoptosis-associated speck-like protein a card expression. Plasmid silencing APE1 gene (APE1shRNA) synthesized packaged into lentiviral. For activating inflammasomes, M2-type THP-1 transfected with lentiviral vector APE1shRNA incubated lipopolysaccharide (LPS) (100 ng/mL)/APE1 inhibitor (E3330, 20 µM) ATP. Electrophoretic mobility shift dual-luciferase reporter interaction between NLRP3 nuclear factor-κB (NF-κB) molecule. Results significantly induced LPS-induced pro-inflammatory cytokine production, including IL-1β, IL18, compared without treatment (P<0.05). promoted inflammasome activation by modulating transcription NLRP3-associated molecules. enhanced regulating caspase-1 improved activity NF-κB, modulation NF-κB. through NF-κB-dependent pathway. Conclusions regulates expression factor NF-κB further promoting secretion IL-1β IL-18 findings provide theoretical experimental bases design tumor-associated macrophage (TAM)-targeted therapy, as target