eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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SCImago Journal & Country Rank
4/2019
vol. 15
 
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abstract:
Experimental research

Urotensin II promotes secretion of LTB4 through 5-lipoxygenase via the UT-ROS-Akt pathway in RAW264.7 macrophages

Dan Lu, Fen Peng, Jun Li, Jing Zhao, Xiaojin Ye, Binghan Li, Wenhui Ding

Arch Med Sci 2019; 15 (4): 1065–1072
Online publish date: 2019/05/15
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Introduction
Urotensin II (UII) is an important vasoactive peptide involved in the pathogenesis of atherosclerosis. Monocytes/macrophages play important roles in every step of atherosclerosis. Although UII has a chemoattractant effect on monocytes, it is unclear whether UII regulates inflammatory responses in macrophages. The present study sought to explore whether UII can promote leukotriene B4 (LTB4) production by macrophages.

Material and methods
The mRNA expression level of leukotriene B4 and 5-lipoxygenase were determined by real-time polymerase chain reaction. The protein level of LTB4 and 5-lipoxygenase expression was assayed by enzyme-linked immunosorbent assay and Western blot, respectively. Western blot analysis was also employed to determine the phosphorylated forms of Akt. Reactive oxygen species (ROS) level was detected by the fluorescent probe 2',7'-dichlorofluorescin diacetate and fluorescence intensity was measured with a multiwell fluorescence plate reader.

Results
Urotensin II promoted LTB4 release and increased 5-lipoxygenase expression in a concentration- and time-dependent manner in RAW264.7 cells. Leukotriene B4 production and 5-lipoxygenase expression were decreased by blocking the UII receptor (UT) with urantide, eliminating ROS with N-acetylcysteine and diphenyliodonium, and inhibiting Akt phosphorylation with LY294002. UII significantly elevated ROS production, whereas urantide, N-acetylcysteine and diphenyliodonium substantially attenuated this effect. UII also enhanced Akt phosphorylation significantly, and this effect was potently inhibited by urantide, N-acetylcysteine, diphenyliodonium and LY294002.

Conclusions
Urotensin II may promote 5-lipoxygenase expression and LTB4 release in RAW264.7 macrophages via UT-ROS-Akt pathways. These results indicate that UII may participate in macrophage activation and suggest a potential new mechanism underlying atherosclerosis.

keywords:

urotensin II, leukotriene B4, macrophages, 5-lipoxygenase, inflammation

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