Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
BMC Immunol. 2010 Oct 19;11:52. doi: 10.1186/1471-2172-11-52.
Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined.
Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to naïve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone.
Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.
白细胞介素-33 是白细胞介素-1 细胞因子家族的一员，其功能由 ST2 受体介导和调节。已经在小鼠巨噬细胞中探索了 IL-33-ST2 的表达和相互作用，但对于 IL-33 对人巨噬细胞的影响知之甚少。检查了 ST2 转录本和蛋白水平的表达，以及 IL-33 对人骨髓来源巨噬细胞中 M1（即经典激活）和 M2（即替代激活）趋化因子标志物表达的介导作用。
人巨噬细胞持续表达膜相关（即 ST2L）和可溶性（即 sST2）ST2 受体。M2（IL-4+IL-13）倾斜刺激显著增加 ST2L 的表达，但两种极化细胞因子处理均未促进 sST2 从这些细胞中释放。当单独添加到未成熟的巨噬细胞时，IL-33 直接增强 CCL3 的表达。与 LPS 联合使用时，IL-33 阻断 M2 趋化因子标志物 CCL18 的表达，但不会改变这些未成熟细胞中 CCL3 的表达。将 IL-33 添加到 M1 巨噬细胞中会显著增加 CCL18 的表达，超过未处理的 M1 巨噬细胞中检测到的表达。同样，用 IL-33 处理的替代激活的人巨噬细胞表现出增强的 CCL18 和 M2 标志物甘露糖受体的表达，超过单独的 M2 巨噬细胞中检测到的表达。
总之，这些数据表明，骨髓来源的人巨噬细胞对 IL-33 的初始反应有利于 M1 趋化因子的产生，而将其添加到极化的人巨噬细胞中则促进或放大 M2 趋化因子的表达。
