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CD147 通过触发 NF-κB 介导的细胞焦亡加重炎症性肠病。

CD147 Aggravated Inflammatory Bowel Disease by Triggering NF-B-Mediated Pyroptosis.

机构信息

The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

出版信息

Biomed Res Int. 2020 Jun 30;2020:5341247. doi: 10.1155/2020/5341247. eCollection 2020.

Abstract

BACKGROUND

Pyroptosis, a novel form of inflammatory programmed cell death, was recently found to be a cause of mucosal barrier defect. In our pervious study, CD147 expression was documented to increase in intestinal tissue of inflammatory bowel disease (IBD).

OBJECTIVE

The aim of this study was to determine the function of serum CD147 in pyroptosis.

METHODS

The study group consisted of 96 cases. The centration of CD147, IL-1, and IL-18 levels in serum was assessed by ELISA. Real-time PCR and WB were performed to analyze the effect of CD147 on pyroptosis.

RESULTS

In this study, our results showed that CD147 induced cell pyroptosis in intestinal epithelial cells (IECs) by enhancement of IL-1 and IL-18 expression and secretion in IECs, which is attributed to activation of inflammasomes, including caspase-1 and GSDMD as well as GSDME, leading to aggregate inflammatory reaction. Mechanically, CD147 promoted phosphorylation of NF-B p65 in IECs, while inhibition of NF-B activity by the NF-B inhibitor BAY11-7082 reversed the effect of CD147 on IL-1 and IL-18 secretion. Most importantly, serum CD147 level is slightly clinically correlated with IL-1, but not IL-18 level.

CONCLUSION

These findings revealed a critical role of CD147 in the patients with IBD, suggesting that blockade of CD147 may be a novel therapeutic strategy for the patients with IBD.

摘要

背景

细胞焦亡是一种新形式的炎症程序性细胞死亡,最近被发现是黏膜屏障缺陷的原因。在我们之前的研究中,已经记录到 CD147 在炎症性肠病(IBD)的肠道组织中表达增加。

目的

本研究旨在确定血清 CD147 在细胞焦亡中的作用。

方法

研究组包括 96 例患者。通过 ELISA 评估血清中 CD147、IL-1 和 IL-18 水平的浓度。通过实时 PCR 和 WB 分析 CD147 对细胞焦亡的影响。

结果

在这项研究中,我们的结果表明,CD147 通过增强 IEC 中 IL-1 和 IL-18 的表达和分泌,诱导肠道上皮细胞(IEC)发生细胞焦亡,这归因于包括 caspase-1 和 GSDMD 以及 GSDME 在内的炎症小体的激活,导致聚集性炎症反应。在机制上,CD147 促进了 IEC 中 NF-B p65 的磷酸化,而 NF-B 抑制剂 BAY11-7082 抑制 NF-B 活性可逆转 CD147 对 IL-1 和 IL-18 分泌的影响。最重要的是,血清 CD147 水平与 IL-1 略有临床相关性,但与 IL-18 水平无关。

结论

这些发现揭示了 CD147 在 IBD 患者中的关键作用,表明阻断 CD147 可能是 IBD 患者的一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c381/7352133/a8e649e83e9f/BMRI2020-5341247.001.jpg

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