巴瑞替丁的免疫调节作用以及激酶钙调蛋白激酶1α（CAMK1α）和受体相互作用蛋白激酶2（RIPK2）的参与。

The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2.

作者信息

Lind Karianne Fredenfeldt, Østerud Bjarne, Hansen Espen, Jørgensen Trond Ø, Andersen Jeanette Hammer

机构信息

a Faculty of Biosciences , Fisheries and Economics, UiT The Arctic University of Norway , Tromsø , Norway .

b Faculty of Health Sciences , UiT The Arctic University of Norway , Breivika , Tromsø , Norway , and.

出版信息

Immunopharmacol Immunotoxicol. 2015;37(5):458-64. doi: 10.3109/08923973.2015.1082584.

DOI:10.3109/08923973.2015.1082584

PMID:26466644

Abstract

BACKGROUND

Barettin is a marine natural compound with reported anti-inflammatory and antioxidant properties. The combination of these effects led us to explore barettin further as an inhibitor of atherosclerosis development.

METHODS

The effect of barettin on MCP-1 and IL-10 secretion from activated immune cells was detected by ELISA. Determination of cell viability of oxidized low-density lipoprotein (oxLDL) and barettin exposed HUVEC cells were investigated by using CellTiter 96® AQ(ueous) One Solution. The kinase inhibition assays were performed using a radioactive ((33)P-ATP) filter binding assay at the University of Dundee, UK.

RESULTS

Barettin reduces the secretion of monocyte chemotactic protein-1 (MCP-1) from LPS-stimulated monocytes, but was not able to prevent oxLDL-induced cell death in HUVEC. Barettin has inhibitory activity against two protein kinases related to inflammation, namely the receptor-interacting serine/threonine kinase 2 (RIPK2) and calcium/calmodulin-dependent protein kinase 1α (CAMK1α). We also demonstrate that barettin reduce the production of the anti-inflammatory cytokine interleukin-10 (IL-10) in a dose and time-dependent manner, possibly by inhibiting CAMK1α.

CONCLUSIONS

The anti-inflammatory activity of barettin is exerted through the regulation of inflammatory mediators such as MCP-1 and IL-10, possibly via inhibition of kinases.

摘要

背景

巴雷廷是一种海洋天然化合物，具有抗炎和抗氧化特性。这些作用的结合促使我们进一步探索巴雷廷作为动脉粥样硬化发展抑制剂的可能性。

方法

通过酶联免疫吸附测定法（ELISA）检测巴雷廷对活化免疫细胞分泌单核细胞趋化蛋白-1（MCP-1）和白细胞介素-10（IL-10）的影响。使用CellTiter 96® AQ（水溶液）单溶液法研究氧化型低密度脂蛋白（oxLDL）和巴雷廷处理的人脐静脉内皮细胞（HUVEC）的细胞活力。激酶抑制试验在英国邓迪大学使用放射性（³³P-ATP）滤膜结合试验进行。

结果

巴雷廷可减少脂多糖（LPS）刺激的单核细胞分泌单核细胞趋化蛋白-1（MCP-1），但无法预防oxLDL诱导的HUVEC细胞死亡。巴雷廷对两种与炎症相关的蛋白激酶具有抑制活性，即受体相互作用丝氨酸/苏氨酸激酶2（RIPK2）和钙/钙调蛋白依赖性蛋白激酶1α（CAMK1α）。我们还证明，巴雷廷可能通过抑制CAMK1α，以剂量和时间依赖性方式减少抗炎细胞因子白细胞介素-10（IL-10）的产生。