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.

中文翻译：

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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

先前的研究表明，半胱天冬酶募集域蛋白 9 (CARD9) 参与严重急性胰腺炎 (SAP) 炎症，干扰其在体内的表达可以抑制炎症。但是，具体机制尚不清楚。本研究旨在发现巨噬细胞中CARD9的相关信号通路。SiRNA干扰技术用于体内外检测腹腔巨噬细胞中CARD9相关信号通路。此外，巨噬细胞中的 Toll 样受体 4 (TLR4) 和膜相关 C 型凝集素-1 (Dectin-1) 通路被专门激活以寻找 CARD9 的上游信号通路。结果显示 SAP 大鼠腹腔巨噬细胞中 CARD9 表达上调（P < .05）。CARD9 siRNA减轻炎症细胞因子，并在体内或体外抑制腹膜巨噬细胞中NF-κB和p38MAPK的磷酸化。同时，CARD9 siRNA降低了腹腔巨噬细胞中CARD9和Bcl10的浓度，TLR4和Dectin-1参与了巨噬细胞中的CARD9信号通路。总之，在 SAP 的巨噬细胞中激活了由 TLR4/Dectin-1-CARD9-NF-κB/p38MAPK 组成的炎症信号通路。巨噬细胞中CARD9表达的阻断可以有效缓解SAP炎症。