A20 functions as a negative regulator in macrophage for DSS-induced colitis.

The function of A20 as a deubiquitinating enzyme in inflammatory diseases and autoimmune diseases has been reported, we therefore aimed to investigate the potential effects of A20 in macrophages and dextran sodium sulfate (DSS)-induced colitis mouse model. Colitis mouse model was induced by DSS treatment. Tnfaip3 mice were crossed with Lyz2-Cre mice to generate A20 myeloid cell-conditional knockout mice. The expression levels of indicated cytokines were analyzed by quantitative reverse transcriptase real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Phosphorylated and total protein levels in nuclear factor kappa B (NF-κB) signaling pathway were detected by Western blot. In the bone marrow of mice, A20 deficiency did not affect macrophage development. In bone marrow-derived macrophages (BMDMs) after lipopolysaccharide (LPS) treatment, A20 deficiency enhanced pro-inflammatory cytokine expression. A20 deficiency in macrophages led to severe symptoms of DSS-induced colitis in mice. A20 deficiency enhanced the NF-κB signaling pathway activity in BMDMs. The effects of A20 deficiency in DSS-induced colitis were suppressed by NF-κB pathway inhibition. A20/inhibitor of NF-κB kinase 2 (IKKβ)-double knockout mice were resistant to DSS-induced colitis. A20 suppresses pro-inflammatory cytokine expression in macrophages through the NF-κB signal pathway and alleviates the pathogenesis of DSS-induced colitis in mice.