Inflammation is a tightly regulated process. During the past decade it has become clear that the resolution of inflammation is an active process and its dysregulation can contribute to chronic inflammation. Several cells and soluble mediators, including lipid mediators, regulate the course of inflammation and its resolution. It is, however, unclear which signals and cells are involved in initiating the resolution process. Macrophages are tissue resident cells and key players in regulating tissue inflammation through secretion of soluble mediators, including lipids. We hypothesize that persistent inflammatory stimuli can initiate resolution pathways in macrophages.

In this study, we detected 21 lipids in LPS-stimulated human monocyte-derived macrophages by liquid chromatography coupled to tandem mass spectrometry. Cyclooxygenase-derived Prostaglandins were observed in the first six hours of stimulation. Interestingly, a switch towards 15-lipoxygenase products, such as the pro-resolving lipid precursors 15-HEPE and 17-HDHA was observed after 24 h. The RNA and protein expression of cyclooxygenase and 15-lipoxygenase were in line with this trend. Treatment with 17-HDHA increased IL-10 production of monocyte-derived macrophages and decreased LTB₄ production by neutrophils, indicating the anti-inflammatory property of this lipid.

These data reveal that monocyte-derived macrophages contribute to the resolution of inflammation in time by the production of pro-resolving lipids after an initial inflammatory stimulus.

炎症是一个严格控制的过程。在过去的十年中，很明显，炎症的消退是一个活跃的过程，其失调可导致慢性炎症。几种细胞和可溶性介体，包括脂质介体，调节炎症的过程及其消退。但是，尚不清楚启动解析过程涉及哪些信号和细胞。巨噬细胞是组织驻留细胞，并且是通过分泌可溶性脂质（包括脂质）来调节组织炎症的关键因素。我们假设持续的炎症刺激可以启动巨噬细胞的解决途径。

在这项研究中，我们通过液相色谱-串联质谱法检测了LPS刺激的人单核细胞衍生巨噬细胞中的21种脂质。在刺激的前六个小时内观察到了环氧合酶衍生的前列腺素。有趣的是，在24小时后，观察到转向15-脂氧合酶产物，例如亲分解脂质前体15-HEPE和17-HDHA。环氧合酶和15-脂氧合酶的RNA和蛋白质表达与这一趋势一致。用17-HDHA处理可增加中性粒细胞的IL-10单核细胞衍生巨噬细胞的产生，并降低LTB _4的产生，表明该脂质具有抗炎特性。

这些数据表明，源自单核细胞的巨噬细胞在最初的炎症刺激后通过促分解脂质的产生，有助于及时解决炎症。