The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States.
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
Immunol Lett. 2018 Jun;198:44-51. doi: 10.1016/j.imlet.2018.03.015. Epub 2018 Mar 30.
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.
A20 是一种锌指蛋白，能有效抑制核因子 (NF)-κB 的激活，下调肿瘤坏死因子-α、白细胞介素 (IL)-1β 和 IL-17 的表达。A20 作为炎症反应的反馈抑制剂也起着至关重要的作用。由于其抑制作用，A20 可能有助于调节因慢性炎症和过度产生促炎细胞因子引起的疾病，如结肠炎。结肠炎患者在肠道中产生高水平的促炎细胞因子。因此，本研究旨在探讨 A20 是否通过降低肠道内的炎症水平来改善实验性结肠炎。在结肠炎诱导后，通过直肠内注射给予小鼠 A20 过表达载体。通过免疫组织化学对肠道切片进行组织学分析评分。通过共聚焦激光扫描显微镜鉴定脾脏组织中 IL-17 和叉头框蛋白 p（FOXP）3 蛋白的表达。通过 Western blot 分析 STAT3 和 NF-κB 信号诱导的蛋白表达。我们发现 A20 降低了结肠炎活动指数评分和肠道的组织学评分。A20 还降低了肠道中的炎症细胞因子水平并增加了结肠长度。此外，A20 过表达下调了 NF-κB 和 STAT3 的激活。A20 还减少了脾脏切片中 CD4 T 细胞中 IL-17 的表达。相反，A20 过表达增强了 CD4 T 细胞中 FOXP3 的表达。这些结果表明，A20 可能通过抑制 NF-κB、磷酸化 STAT3 和 IL-17 来减少炎症从而抑制结肠炎的进展。
