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

ABSTRACT

OBJECTIVE: To 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. METHODS: Traumatic 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). RESULTS: Trauma 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. CONCLUSIONS: A20 zinc finger protein plays an anti-inflammatory role and protects against liver injury associated with trauma combined with LPS challenge.