Role of CARD9 in inflammatory signal pathway of peritoneal macrophages in severe acute pancreatitis.
Role of CARD9 in inflammatory signal pathway of peritoneal macrophages in severe acute pancreatitis.
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CARD9在重症急性胰腺炎腹腔巨噬细胞炎症信号通路中的作用
DOI：
10.1111/jcmm.15559
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Wang J;Tian J;He YH;Yang ZW;Wang L;Lai YX;Xu P
前期研究发现caspase募集结构域蛋白9 （caspase募集结构域蛋白9，CARD9）参与了严重急性胰腺炎（severe acute pancreatitis SAP）炎症反应，在体内干扰其表达可抑制炎症反应。然而，具体的机制尚不清楚。本研究旨在发现巨噬细胞中CARD9的相关信号通路。在体内和体外应用SiRNA干扰技术检测腹膜巨噬细胞中CARD9相关信号通路。此外，巨噬细胞中Toll样受体4 （TLR4）和膜相关C型凝集素1 （Dectin‐1）通路被特别激活，以寻找CARD9的上游信号通路。结果显示，SAP大鼠腹膜巨噬细胞中CARD9的表达受到调节（P < 0.05）。在体内和体外实验中，CARD9 siRNA可减轻腹膜巨噬细胞的炎症因子，抑制NF - κB和p38MAPK的磷酸化。同时，CARD9 siRNA降低了腹膜巨噬细胞中CARD9和Bcl10的浓度，TLR4和Dectin‐1参与了巨噬细胞中CARD9的信号通路。综上所述，SAP巨噬细胞中存在TLR4/Dectin‐1‐CARD9‐NF‐κB/p38MAPK激活的炎症信号通路，阻断巨噬细胞中CARD9的表达可有效缓解SAP炎症。
Previous studies revealed that caspase recruitment domain protein 9 (CARD9) was involved in severe acute pancreatitis (SAP) inflammation and that interfering with its expression in vivo could inhibit inflammation. However, the specific mechanism is unknown. This study aimed to discover the related signal pathways of CARD9 in macrophages. SiRNA interference technology was used in vivo and in vitro to detect CARD9‐related signal pathways in peritoneal macrophages. Furthermore, Toll‐like receptor 4 (TLR4) and membrane‐associated C‐type lectin‐1 (Dectin‐1) pathways in macrophages were activated specially to looking for the upstream signal path of CARD9. Results showed up‐regulation of CARD9 expression in peritoneal macrophages of SAP rats (P < .05). CARD9 siRNA alleviated inflammatory cytokines, and inhibited the phosphorylation of NF‐κB and p38MAPK in peritoneal macrophages in vivo or in vitro. Meanwhile, CARD9 siRNA reduced the concentration of CARD9 and Bcl10 in peritoneal macrophages, and TLR4 and Dectin‐1 took part in CARD9 signal pathways in macrophages. In conclusion, there is an inflammation signal pathway comprised of TLR4/Dectin‐1‐CARD9‐NF‐κB/p38MAPK activated in macrophages in SAP. Blockade of CARD9 expression in macrophages can effectively alleviate SAP inflammation.
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