Rolin Johannes, Vego Heidi, Maghazachi Azzam A
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo 0317, Norway.
Toxins (Basel). 2014 Sep 23;6(9):2840-56. doi: 10.3390/toxins6092840.
Lipids through regulation of chronic inflammation play key roles in the development of various diseases. Here, we report that a mixed population of human primary monocytes migrated towards LPC, as well as oxidized linoleic acid isoforms 9-S-HODE, 9-R-HODE and 13-R-HODE. Incubation with 9-R-HODE, 13-R-HODE and LPC resulted in increased expression of CXCR4, the receptor for SDF-1α/CXCL12, correlated with increased monocyte migration towards SDF-1α/CXCL12. Further, we report increased expression of CCR9, the receptor for TECK/CCL25, after stimulation with these lipids. Upon examining the migratory response towards TECK/CCL25, it was observed that an increase in CCR9 expression upon pre-treatment with 9-S-HODE, 9-R-HODE, 13-R-HODE and LPC resulted in increased migration of monocytes expressing CCR9. Only LPC but not any other lipid examined increased the influx of intracellular Ca2+ in monocytes. Finally, 9-S-HODE, 9-R-HODE, 13-R-HODE, or LPC inhibited the release of IL-6 from monocytes suggesting that these lipids may play important role in controlling inflammatory responses.
脂质通过调节慢性炎症在多种疾病的发展中起关键作用。在此，我们报道人类原代单核细胞的混合群体向溶血磷脂酰胆碱（LPC）以及氧化亚油酸异构体9 - S - 羟基十八碳二烯酸（9 - S - HODE）、9 - R - 羟基十八碳二烯酸（9 - R - HODE）和13 - R - 羟基十八碳二烯酸（13 - R - HODE）迁移。与9 - R - HODE、13 - R - HODE和LPC孵育导致趋化因子受体4（CXCR4）表达增加，CXCR4是基质细胞衍生因子1α/趋化因子CXC配体12（SDF - 1α/CXCL12）的受体，这与单核细胞向SDF - 1α/CXCL12的迁移增加相关。此外，我们报道在用这些脂质刺激后，胸腺表达趋化因子（TECK）/趋化因子C - C基序配体25（CCL25）的受体CCR9表达增加。在检测对TECK/CCL25的迁移反应时，观察到用9 - S - HODE、9 - R - HODE、13 - R - HODE和LPC预处理后CCR9表达增加导致表达CCR9的单核细胞迁移增加。只有LPC而非其他任何检测的脂质增加了单核细胞内钙离子的流入。最后，9 - S - HODE、9 - R - HODE、13 - R - HODE或LPC抑制单核细胞中白细胞介素6（IL - 6）的释放，表明这些脂质可能在控制炎症反应中起重要作用。
