| First Author | Pu T | Year | 2021 |
| Journal | Int Immunopharmacol | Volume | 97 |
| Pages | 107804 | PubMed ID | 34062371 |
| Mgi Jnum | J:313411 | Mgi Id | MGI:6764687 |
| Doi | 10.1016/j.intimp.2021.107804 | Citation | Pu T, et al. (2021) A20 functions as a negative regulator in macrophage for DSS-induced colitis. Int Immunopharmacol 97:107804 |
| abstractText | 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(fl/fl) 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-kappaB) 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-kappaB signaling pathway activity in BMDMs. The effects of A20 deficiency in DSS-induced colitis were suppressed by NF-kappaB pathway inhibition. A20/inhibitor of NF-kappaB kinase 2 (IKKbeta)-double knockout mice were resistant to DSS-induced colitis. A20 suppresses pro-inflammatory cytokine expression in macrophages through the NF-kappaB signal pathway and alleviates the pathogenesis of DSS-induced colitis in mice. |
