A20 overexpression alleviates pristine-induced lupus nephritis by inhibiting the NF-κB and NLRP3 inflammasome activation in macrophages of mice.

BACKGROUND: Lupus nephritis is an autoimmune inflammatory disease and urgently needs effective anti-inflammation therapies. A20, tumor necrosis factor alpha induced protein 3 (TNFAIP3), is a key negative regulator of inflammation, however whether A20 can regulate lupus nephritis has not been clarified. This study aimed at investigating the potential therapeutic effect of A20 on renal inflammation in mouse pristine model oflupus. METHODOLOGY/PRINCIPAL
FINDINGS: Female BALB/c mice were intraperitoneally injected with pristine to establish lupus renal injury. The levels of serum IL-1β, IL-6 and autoantibodies and the degrees of renal injury and CCL2 and F4/80 levels were measured. The levels of the NF-κB and NLRP3 inflammasome activation in peritoneal macrophages were determined. We found that injection with pristine increased the levels of serum IL-1β, IL-6, autoantibodies and CCL20 and F4/80 expression in the kidney and induced renal injury, accompanied by enhancing the NF-κB and NLRP3 inflammasome activation in macrophages of mice. In contrast, treatment with Ad-A20, but not with Ad-control, significantly mitigated pristine-induced inflammatory responses and renal injury,and reduced the NF-κB and NLRP3 inflammasome activation in macrophages in mice. CONCLUSION/SIGNIFICANCE: Our data indicated that induction of A20 overexpression inhibited pristane induced lupus inflammation and renal injury in mice and may be a new therapeutic strategy for treatment of lupus nephritis.