红景天苷通过NF-κB/MAPK和STAT3信号通路调节脂多糖激活的肠上皮细胞中白细胞介素-6和防御素的表达。

Salidroside regulates the expressions of IL-6 and defensins in LPS-activated intestinal epithelial cells through NF-κB/MAPK and STAT3 pathways.

作者信息

Wang Jiawen, Pan Yibin, Cao Yongqing, Zhou Wei, Lu Jingen

机构信息

Department of Anal & Intestinal Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R.China.

出版信息

Iran J Basic Med Sci. 2019 Jan;22(1):31-37. doi: 10.22038/ijbms.2018.26994.6602.

OBJECTIVES

To reveal the detailed mechanism underlying the functions of salidroside on the inflammation of intestinal epithelial cells during IBD.

MATERIALS AND METHODS

Quantitative real-time PCR was employed to assess the expression of IL-6, IL-10, and α-defensins 5 and 6. ELISA assay was performed to measure the secretion of IL-6 and IL-10. MTT assay was used to determine the cell viability and proliferation. Western blot was used to assess the phosphorylation of NF-kB, Erk1/2, JNK, P38, JAK2, and STAT3.

RESULTS

Salidroside impaired the proliferation of intestinal epithelial cells at high concentrations (< 0.05) and down-regulated interleukin-6 (IL-6) production induced by LPS (<0.05). Western blot results showed that salidroside repressed the phosphorylation of NF-kB, Erk1/2, JNK, P38, JAK2 and STAT3 (<0.05) and attenuated the activation of NF-κB, MAPK, and STAT3 pathways. Moreover, the expressions of α-defensin 5 and 6 were rescued by salidroside after LPS or SAC triggering (<0.05).

CONCLUSION

In summary, salidroside suppressed the expression of IL-6 and elevated the expression of defensins in LPS-activated intestinal epithelial cells through NF-κB/MAPK and STAT3 pathways. The mechanism revealed here may be potentially useful for the treatment of IBD with salidroside.

目的

揭示红景天苷在炎症性肠病（IBD）期间对肠上皮细胞炎症发挥作用的详细机制。

材料与方法

采用定量实时聚合酶链反应（qRT-PCR）评估白细胞介素-6（IL-6）、白细胞介素-10以及α-防御素5和6的表达。进行酶联免疫吸附测定（ELISA）以检测IL-6和IL-10的分泌。采用噻唑蓝（MTT）比色法测定细胞活力和增殖情况。使用蛋白质免疫印迹法评估核因子-κB（NF-κB）、细胞外信号调节激酶1/2（Erk1/2）、应激活化蛋白激酶（JNK）、p38丝裂原活化蛋白激酶（P38）、Janus激酶2（JAK2）和信号转导子与转录激活子3（STAT3）的磷酸化水平。

结果

红景天苷在高浓度时（<0.05）损害肠上皮细胞的增殖，并下调脂多糖（LPS）诱导的白细胞介素-6（IL-6）产生（<0.05）。蛋白质免疫印迹结果显示，红景天苷抑制NF-κB、Erk1/2、JNK、P38、JAK2和STAT3的磷酸化（<0.05），并减弱NF-κB、丝裂原活化蛋白激酶（MAPK）和STAT3信号通路的激活。此外，在LPS或链球菌抗生物素C（SAC）刺激后，红景天苷使α-防御素5和6的表达得到恢复（<0.05）。