A20 ameliorates inflammatory bowel disease in mice via inhibiting NF-κB and STAT3 activation.

A20 is a zinc finger protein that effectively inhibits the activation of nuclear factor (NF)-κB to downregulate the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-17. A20 also plays a crucial role as a feedback inhibitor of the inflammatory response. Due to its inhibitory role, A20 may be useful in regulating diseases resulting from chronic inflammation and excessive pro-inflammatory cytokine production, such as colitis. Patients with colitis produce high levels of pro-inflammatory cytokines in the intestine. Therefore, this study aimed to investigate whether A20 improves experimental colitis by reducing high levels of inflammation in the intestine. An A20 overexpression vector was administered to mice by intrarectal injection after colitis induction. Histological analysis by immunohistochemistry was used to score sections of the intestine. Confocal laser scanning microscopy was used to identify the expression of IL-17 and forkhead box p (FOXP) 3 protein in spleen tissues. Protein expression induced by STAT3 and NF-κB signaling was analyzed by western blot. We found that A20 reduced the colitis activity index score and the histological score of the intestine. A20 also decreased inflammatory cytokine levels in the intestine and increased colon length. Additionally, A20 overexpression downregulated the activation of NF-kB and STAT3. A20 also reduced IL-17 expression in CD4 T cells from spleen sections. In contrast, A20 overexpression enhanced the expression of FOXP3 in CD4 T cells. These results suggest that A20 may inhibit the progression of colitis by decreasing inflammation via inhibition of NF-κB, phosphorylated STAT3, and IL-17.