Department of Rheumatology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
J Immunol. 2020 Nov 15;205(10):2840-2849. doi: 10.4049/jimmunol.1801653. Epub 2020 Oct 2.
Polyunsaturated fatty acids (PUFAs) and their metabolites are potent regulators of inflammation. Generally, omega ()-3 PUFAs are considered proresolving whereas -6 PUFAs are classified as proinflammatory. In this study, we characterized the inflammatory response in murine peritonitis and unexpectedly found the accumulation of adrenic acid (AdA), a poorly studied -6 PUFA. Functional studies revealed that AdA potently inhibited the formation of the chemoattractant leukotriene B (LTB), specifically in human neutrophils, and this correlated with a reduction of its precursor arachidonic acid (AA) in free form. AdA exposure in human monocyte-derived macrophages enhanced efferocytosis of apoptotic human neutrophils. In vivo, AdA treatment significantly alleviated arthritis in an LTB-dependent murine arthritis model. Our findings are, to our knowledge, the first to indicate that the -6 fatty acid AdA effectively blocks production of LTB by neutrophils and could play a role in resolution of inflammation in vivo.
多不饱和脂肪酸 (PUFAs) 及其代谢产物是炎症的有效调节剂。一般来说，ω ()-3 PUFAs 被认为是促解决的，而 -6 PUFAs 被归类为促炎的。在这项研究中，我们描述了鼠腹膜炎中的炎症反应，出人意料地发现了一种研究较少的 -6 PUFA，即花生四烯酸 (AdA) 的积累。功能研究表明，AdA 强烈抑制趋化因子白三烯 B (LTB) 的形成，特别是在人类中性粒细胞中，这与游离形式的前体花生四烯酸 (AA) 减少相关。AdA 暴露于人单核细胞衍生的巨噬细胞中增强了凋亡的人中性粒细胞的吞噬作用。在体内，AdA 治疗可显著缓解依赖 LTB 的小鼠关节炎模型中的关节炎。据我们所知，我们的研究结果首次表明 -6 脂肪酸 AdA 可有效阻止中性粒细胞产生 LTB，并可能在体内炎症消退中发挥作用。
