An anti-inflammatory role of A20 zinc finger protein during trauma combined with endotoxin challenge

ObjectiveTo investigate the anti-inflammatory role of A20 zinc finger protein during trauma combined with bacterial endotoxin challenge and explore the molecular mechanism underlying this process.MethodsTraumatic bone impact injury was induced in the hind limbs of mice. One hour after injury, mice were challenged with purified gram-negative bacterial endotoxins, lipopolysaccharides (LPSs), by tail vein injection. Effects on A20 messenger RNA and protein expressions were assessed by reverse transcription–polymerase chain reaction and Western blotting, respectively. A20 recombinant adenoviruses, full-length (pAdA20 1-775) and N-terminal mutant (pAdA20 1-367), were constructed and used to infect RAW264.7 macrophage cells or mice. Responses in the tumor necrosis factor α (TNF-α)–nuclear factor κB (NF-κB) signaling pathway were evaluated by enzyme-linked immunosorbent assay (for TNF-α) and electrophoretic mobility shift assay (for NF-κB).ResultsTrauma combined with LPS challenge and LPS challenge alone dramatically promoted A20 expression in mouse liver tissues. LPS challenge increased A20 messenger RNA levels appreciably in RAW264.7 cells within 1 h. Full-length A20 recombinant adenoviruses (pAdA20 1-775) suppressed NF-κB activity and TNF-α expression and protected against liver damage and animal death otherwise induced by trauma combined with LPS challenge.ConclusionsA20 zinc finger protein plays an anti-inflammatory role and protects against liver injury associated with trauma combined with LPS challenge.