The synthetic triterpenoid (CDDO-Im) inhibits STAT3, as well as IL-17, and improves DSS-induced colitis in mice
The synthetic triterpenoid (CDDO-Im) inhibits STAT3, as well as IL-17, and improves DSS-induced colitis in mice
复制标题
DOI：
10.1007/s10787-014-0203-2
复制
发表时间：
2014-12-01
影响因子：
5.8
通讯作者：
Liby, Karen T.
中科院分区：
文献类型：
--
作者：
Fitzpatrick, Leo R.;Stonesifer, Elizabeth;Liby, Karen T.
介绍合成三萜类化合物抑制IL-17和改善小鼠自身免疫性疾病。三萜类化合物1-[2-氰基-3，12-二氧代齐墩果-1，9（11）-二烯-28酰基]咪唑（CDDO-Im）也能抑制信号转导和转录激活因子3（STAT 3）的活化。（2）研究口服CDDO-Im是否能改善DSS诱导的小鼠结肠炎。用三硝基苯磺酸或葡聚糖硫酸钠（DSS）在啮齿动物中诱导结肠炎。结肠炎诱导后5或6天收集结肠条。将脾细胞或结肠条暴露于CDDO-Im（0.5-2 μ M）和IL-23 + IL-1 μ M。在48或24小时后收集上清液，并通过ELISA测量IL-17。使用DSS结肠炎模型，在5天的时间内向小鼠口服给予媒介物或CDDO-Im（20 mg/kg）。结果CDDO-Im体外处理可抑制脾细胞和结肠条分泌IL-17。ic 50值
Introduction Synthetic triterpenoids inhibit IL-17 and improve autoimmune disease in mice. A prototype triter-penoid, 1-[2-cyano-3-, 12-dioxooleana-1,9(11)-dien-28oyl] imidazole (CDDO-Im), also inhibits signal transducer and activator of transcription 3 (STAT3) activation.Aims The goals of our study were twofold: (1) To determine if ex vivo treatment with CDDO-Im attenuated colonic IL-17 secretion from isolated splenocytes and colonic strips; (2) To determine if oral treatment with CDDO-Im improved DSS-induced colitis in mice.Methods Splenocytes were isolated from male Balb/c mice. Colitis was induced in rodents, with either trinitrobenzene sulfonic acid or dextran sulfate sodium (DSS). Colonic strips were collected 5 or 6 days after colitis induction. Splenocytes or colonic strips were exposed to CDDO-Im (0.5-2 mu M) concomitantly with IL-23 + IL-1 mu. Supernatants were collected after 48 or 24 h, and IL-17 was measured by ELISA. Using a DSS colitis model, mice were dosed orally with vehicle or CDDO-Im (20 mg/kg) over a 5-day period. Subsequently, various parameters of colitis were determined on study day 6.Results Ex vivo treatment with CDDO-Im inhibited IL-17 secretion from splenocytes and colonic strips. The IC50 values were