白细胞介素-1β抑制脂多糖刺激的马全血中 5-脂氧合酶的合成。

Interleukin-1β inhibits synthesis of 5-lipooxygenase in lipopolysaccharide-stimulated equine whole blood.

机构信息

University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA 19348, USA.

University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA 19348, USA; PA Equine Toxicology & Research Center, West Chester University, Department of Chemistry, 220 East Rosedale Avenue, West Chester, PA 19382, USA.

出版信息

Prostaglandins Other Lipid Mediat. 2014 Jan;108:9-22. doi: 10.1016/j.prostaglandins.2014.01.001. Epub 2014 Feb 12.

DOI:10.1016/j.prostaglandins.2014.01.001

PMID:24530239

Abstract

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine. It induces the synthesis of prostaglandin E2 (PGE2) catalyzed by cyclooxygenase (COX) and microsomal prostaglandin E synthase (m-PGES). Besides its pro-inflammatory properties, PGE2 also exhibits anti-inflammatory properties by inhibiting synthesis of 5-lipooxygenase (5-LO) products which are in themselves, pro-inflammatory mediators. Thus, inhibition of 5-LO products is beneficial in regulating immune-responses and pro-inflammatory processes. To investigate the hypothesis that IL-1β is responsible for the increase in the synthesis of PGE2 and in the reduction of 5-LO products, equine whole blood (EWB) was treated with lipopolysaccharide (LPS). In vitro treatment of EWB with LPS resulted in increased expression of IL-1β while expression of 5-LO was suppressed. Quantification of eicosanoids using liquid-chromatography-mass spectrometry/multiple reaction monitoring (LC-MS/MRM) showed increased concentrations of prostaglandins and decreased 5-LO products in LPS-treated EWB. Pretreatment of EWB with IL-1β followed by calcium ionophore A23187 (CI) reduced synthesis of 5-LO products. However, pretreatment of EWB with COX-2 inhibitor (NS-398) or m-PGES-1 inhibitor (CAY 10526) and IL-1β followed with CI resulted in a significant (p<0.0001) increase in 5-LO products. Pretreatment of EWB with phospholipase C inhibitor (U73122) followed with LPS reduced PGE2 production but increased 5-LO products. The result of this study indicated that increased PGE2 production led to reduction in 5-LO products in LPS-treated EWB via IL-1β. However, other pathways, cytokines and mediators may be involved in inhibiting 5-LO products but the present study did not include those other potential pathways. Inhibition of 5-LO products by PGE2 in EWB may regulate the initiation and pathogenesis of inflammatory responses in the horse.

摘要

白细胞介素-1β（IL-1β）是一种促炎细胞因子。它诱导前列腺素 E2（PGE2）的合成，由环氧化酶（COX）和微粒体前列腺素 E 合酶（m-PGES）催化。除了其促炎特性外，PGE2 还通过抑制 5-脂氧合酶（5-LO）产物的合成来发挥抗炎特性，而 5-LO 产物本身就是促炎介质。因此，抑制 5-LO 产物有益于调节免疫反应和促炎过程。为了研究假设，即 IL-1β 负责增加 PGE2 的合成和减少 5-LO 产物，用脂多糖（LPS）处理马全血（EWB）。LPS 体外处理 EWB 导致 IL-1β 的表达增加，而 5-LO 的表达受到抑制。使用液相色谱-质谱/多重反应监测（LC-MS/MRM）对类二十烷酸进行定量，显示 LPS 处理的 EWB 中前列腺素浓度增加，5-LO 产物减少。用白细胞介素-1β（IL-1β）预处理 EWB ，然后用钙离子载体 A23187（CI）处理，可减少 5-LO 产物的合成。然而，用 COX-2 抑制剂（NS-398）或 m-PGES-1 抑制剂（CAY 10526）预处理 EWB ，然后用 IL-1β 和 CI 处理，可导致 5-LO 产物显著增加（p<0.0001）。用磷脂酶 C 抑制剂（U73122）预处理 EWB ，然后用 LPS 处理，可减少 PGE2 的产生，但增加 5-LO 产物。本研究结果表明，在 LPS 处理的 EWB 中，IL-1β 导致 PGE2 产量增加，导致 5-LO 产物减少。然而，其他途径、细胞因子和介质可能参与抑制 5-LO 产物，但本研究未包括这些其他潜在途径。PGE2 在 EWB 中对 5-LO 产物的抑制可能调节马中炎症反应的启动和发病机制。