Interleukin-32 induces the differentiation of monocytes into macrophage-like cells
Interleukin-32 induces the differentiation of monocytes into macrophage-like cells
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DOI：
10.1073/pnas.0712381105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Kim, Soo-Hyun
中科院分区：
文献类型：
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作者：
Netea, Mihai G.;Lewis, Eli C.;Kim, Soo-Hyun
单核细胞从骨髓迁移到外周血后，进入组织并分化为巨噬细胞，巨噬细胞是免疫系统的原型清道夫。通过摄取和杀死微生物和清除细胞碎片，巨噬细胞也处理抗原，作为建立特定免疫反应的第一步。IL-32是一种通过p38-MAPK和NF-kappa b诱导促炎细胞因子和趋化因子的细胞因子。在本研究中，我们证明IL-32诱导人血液单核细胞和THP-1白血病细胞分化为巨噬细胞样细胞，对活菌具有功能性吞噬活性。Muramyl dipepide （MDP）是胞内核寡聚结构域（NOD） 2受体的配体，它对单核细胞向巨噬细胞的分化没有单独的影响，但可以通过IL-32增强单核细胞向巨噬细胞的分化。出乎意料的是，IL-32逆转了GM-CSF/ il -4诱导的树突状细胞向巨噬细胞样细胞的分化。IL-32诱导TNF α、IL-1 β和IL-6是由p38-MAPK介导的，而IL-32诱导的单核细胞向巨噬细胞分化是通过非凋亡、caspase-3依赖性机制介导的。因此，IL-32不仅通过诱导促炎细胞因子参与宿主应答，而且通过将单核细胞分化为巨噬细胞样细胞直接影响特异性免疫。
After emigration from the bone marrow to the peripheral blood, monocytes enter tissues and differentiate into macrophages, the prototype scavenger of the immune system. By ingesting and killing microorganisms and removing cellular debris, macrophages also process antigens as a first step in mounting a specific immune response. IL-32 is a cytokine inducing proinflammatory cytokines and chemokines via p38-MAPK and NF-kappa B. In the present study, we demonstrate that IL-32 induces differentiation of human blood monocytes as well as THP-1 leukemic cells into macrophage-like cells with functional phagocytic activity for live bacteria. Muramyl dipepide (MDP), the ligand for the intracellular nuclear oligomerization domain (NOD) 2 receptor, has no effect on differentiation alone but augments the monocyte-to-macrophage differentiation by IL-32. Unexpectedly, IL-32 reversed GM-CSF/IL-4-induced dendritic cell differentiation to macrophage-like cells. Whereas the induction of TNF alpha, IL-1 beta, and IL-6 by IL-32 is mediated by p38-MAPK, IL-32-induced monocyte-to-macrophage differentiation is mediated through nonapoptotic, caspase-3-dependent mechanisms. Thus, IL-32 not only contributes to host responses through the induction of proinflammatory cytokines but also directly affects specific immunity by differentiating monocytes into macrophage-like cells.