EETs Attenuate Ox-LDL-Induced LTB4 Production and Activity by Inhibiting p38 MAPK Phosphorylation and 5-LO/BLT1 Receptor Expression in Rat Pulmonary Arterial Endothelial Cells
| Autor: | Qiang-min Xie, Jun-xia Jiang, Shui-juan Zhang, Hui-juan Shen, Yao-kang Xiong, Xiao-Feng Yan, Yong-liang Jia, Xi-xi Lin, Yan-hong Sun |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Epoxygenase Male Leukotriene B4 Receptor expression Vasodilator Agents Blotting Western Receptors Leukotriene B4 lcsh:Medicine Biology Pulmonary Artery Real-Time Polymerase Chain Reaction p38 Mitogen-Activated Protein Kinases Rats Sprague-Dawley chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid Animals RNA Messenger Phosphorylation lcsh:Science Receptor Protein kinase A Cells Cultured Inflammation Leukotriene Multidisciplinary Arachidonate 5-Lipoxygenase Reverse Transcriptase Polymerase Chain Reaction lcsh:R Molecular biology Cell biology Rats Lipoproteins LDL chemistry Arachidonate 5-lipoxygenase biology.protein lcsh:Q lipids (amino acids peptides and proteins) Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 6, p e0128278 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Cytochrome P-450 epoxygenase (EPOX)-derived epoxyeicosatrienoic acids (EETs), 5-lipoxygenase (5-LO), and leukotriene B4 (LTB4), the product of 5-LO, all play a pivotal role in the vascular inflammatory process. We have previously shown that EETs can alleviate oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation in primary rat pulmonary artery endothelial cells (RPAECs). Here, we investigated whether ox-LDL can promote LTB4 production through the 5-LO pathway. We further explored how exogenous EETs influence ox-LDL-induced LTB4 production and activity. We found that treatment with ox-LDL increased the production of LTB4 and further led to the expression and release of both monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 (ICAM-1). All of the above ox-LDL-induced changes were attenuated by the presence of 11,12-EET and 14,15-EET, as these molecules inhibited the 5-LO pathway. Furthermore, the LTB4 receptor 1 (BLT1 receptor) antagonist U75302 attenuated ox-LDL-induced ICAM-1 and MCP-1/CCL2 expression and production, whereas LY255283, a LTB4 receptor 2 (BLT2 receptor) antagonist, produced no such effects. Moreover, in RPAECs, we demonstrated that the increased expression of 5-LO and BLT1 following ox-LDL treatment resulted from the activation of nuclear factor-κB (NF-κB) via the p38 mitogen-activated protein kinase (MAPK) pathway. Our results indicated that EETs suppress ox-LDL-induced LTB4 production and subsequent inflammatory responses by downregulating the 5-LO/BLT1 receptor pathway, in which p38 MAPK phosphorylation activates NF-κB. These results suggest that the metabolism of arachidonic acid via the 5-LO and EPOX pathways may present a mutual constraint on the physiological regulation of vascular endothelial cells. |
| Databáze: | OpenAIRE |
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