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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1{beta} and IL-6 production through a caspase 1-dependent mechanism.
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IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1{beta} and IL-6 production through a caspase 1-dependent mechanism.

机译：IL-32通过半胱天冬酶1依赖性机制与核苷酸低聚结构域（NOD）1和NOD2配体协同作用，以产生IL-1 {beta}和IL-6。

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摘要

The activation of innate immunity requires the amplification of signals induced by pattern-recognition receptors for bacterial products. We have investigated the role of the newly described cytokine IL-32 in the amplification of cytokine production induced by the two most clinically relevant families of microbial receptors, the cell-surface Toll-like receptors (TLRs) and the intracellular nuclear oligomerization domain (NOD) receptor family. IL-32 synergized with the NOD1- and NOD2-specific muropeptides of peptidoglycans for the release of IL-1beta and IL-6 (a 3- to 10-fold increase). In contrast, IL-32 did not influence the cytokine production induced via TLRs. The synergistic effect of IL-32 and synthetic muramyl dipeptide (MDP) on cytokine production was absent in the cells of patients with Crohn's disease bearing the NOD2 frameshift mutation 3020insC, demonstrating that the IL-32/MDP synergism depends on NOD2. This in vitro synergism between IL-32 and NOD2 ligands was consistent with a marked constitutive expression of IL-32 in human colon epithelial tissue. In addition, the potentiating effect of IL-32 on the cytokine production induced by the synthetic muropeptide FK-156 was absent in NOD1-deficient macrophages, supporting the interaction between IL-32 and NOD1 pathways. When specific caspase inhibitors were used, the synergism between IL-32 and MDP/NOD2 depended on the activation of caspase 1. Only additive effects of IL-32 and muropeptides were observed for TNF-alpha production. The modulation of intracellular NOD2 pathways by IL-32, but not cell-surface TLRs, and the marked expression of IL-32 in colon mucosa suggest a role of IL-32 in the pathogenesis of Crohn's disease.
机译：先天免疫的激活需要放大细菌产品的模式识别受体诱导的信号。我们已经研究了新描述的细胞因子IL-32在由两个临床上最相关的微生物受体家族（细胞表面Toll样受体（TLR）和细胞内核寡聚域（NOD））诱导的细胞因子生成放大中的作用）受体家族。 IL-32与肽聚糖的NOD1和NOD2特异性多聚肽协同作用，可释放IL-1beta和IL-6（增加3至10倍）。相反，IL-32不影响通过TLR诱导的细胞因子产生。在患有带有NOD2移码突变3020insC的克罗恩病患者的细胞中，没有IL-32和合成的鼠王酰胺二肽（MDP）对细胞因子产生的协同作用，这表明IL-32 / MDP的协同作用取决于NOD2。 IL-32和NOD2配体之间的这种体外协同作用与人结肠上皮组织中IL-32的明显组成型表达是一致的。此外，在缺乏NOD1的巨噬细胞中缺乏IL-32对合成的多肽FK-156诱导的细胞因子产生的增强作用，从而支持了IL-32与NOD1途径之间的相互作用。当使用特定的半胱天冬酶抑制剂时，IL-32与MDP / NOD2之间的协同作用取决于半胱天冬酶1的激活。仅观察到IL-32和多肽对TNF-α产生加和作用。 IL-32对细胞内NOD2途径的调节，但对细胞表面TLR的调节不大，以及结肠粘膜中IL-32的明显表达表明IL-32在克罗恩病的发病机理中具有重要作用。

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