LPS induces ALOX5 promoter activation and 5-lipoxygenase expression in human monocytic cells
Copyright © 2020 Elsevier Ltd. All rights reserved..
5-lipoxygenase (5-LO), coded by the ALOX5 gene, is expressed in leukocytes and catalyzes the formation of leukotrienes, pro-inflammatory lipid mediators. Leukotrienes are central to immune responses, but are also involved in inflammatory disorders and 5-LO expression is associated with leukemia stem cell survival. It is therefore important to understand mechanisms that control 5-LO expression. This study investigated the control of 5-LO expression and leukotriene biosynthesis following the maturation of human monocytic cells. MonoMac-1 (MM1) and THP-1 cells were incubated for up to 72 h with or without LPS and TGF-β. LPS, but not TGF-β, increased CD14 expression in both MM1 and THP-1 cells. Incubation with LPS (100 ng/ml) and TGF-β (1 ng/ml) synergistically increased the capacity of MM1 cells to produce 5-LO products from undetectable levels to 40±5 pmol/106 cells. 5-LO product biosynthesis in THP-1 cells increased 25-fold. A synergistic effect of LPS and TGF-β was measured with increases in 5-LO mRNA of 54- and 13-fold in MM1 and THP-1 cells, respectively. 5-LO protein expression increased significantly in both MM1 and THP-1 cells. ALOX5 promoter activity was significantly elevated >2-fold in both cell lines following LPS treatment, but TGF-β was without effect. The main 5-LO products were cysteinyl-leukotrienes, however LPS and TGF-β did not impact on the capacity of the cells to metabolize leukotriene A4. Overall, this study demonstrates that receptor-mediated stimulation of MM1 and THP-1 cells by LPS is associated with increased 5-LO expression. This represents a new mechanism by which leukotriene biosynthesis can be modulated by pathological agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:154 |
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| Enthalten in: |
Prostaglandins, leukotrienes, and essential fatty acids - 154(2020) vom: 21. März, Seite 102078 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Poirier, Samuel J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.09.2020 Date Revised 21.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.plefa.2020.102078 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Copyright © 2020 Elsevier Ltd. All rights reserved. | ||
| 520 | |a 5-lipoxygenase (5-LO), coded by the ALOX5 gene, is expressed in leukocytes and catalyzes the formation of leukotrienes, pro-inflammatory lipid mediators. Leukotrienes are central to immune responses, but are also involved in inflammatory disorders and 5-LO expression is associated with leukemia stem cell survival. It is therefore important to understand mechanisms that control 5-LO expression. This study investigated the control of 5-LO expression and leukotriene biosynthesis following the maturation of human monocytic cells. MonoMac-1 (MM1) and THP-1 cells were incubated for up to 72 h with or without LPS and TGF-β. LPS, but not TGF-β, increased CD14 expression in both MM1 and THP-1 cells. Incubation with LPS (100 ng/ml) and TGF-β (1 ng/ml) synergistically increased the capacity of MM1 cells to produce 5-LO products from undetectable levels to 40±5 pmol/106 cells. 5-LO product biosynthesis in THP-1 cells increased 25-fold. A synergistic effect of LPS and TGF-β was measured with increases in 5-LO mRNA of 54- and 13-fold in MM1 and THP-1 cells, respectively. 5-LO protein expression increased significantly in both MM1 and THP-1 cells. ALOX5 promoter activity was significantly elevated >2-fold in both cell lines following LPS treatment, but TGF-β was without effect. The main 5-LO products were cysteinyl-leukotrienes, however LPS and TGF-β did not impact on the capacity of the cells to metabolize leukotriene A4. Overall, this study demonstrates that receptor-mediated stimulation of MM1 and THP-1 cells by LPS is associated with increased 5-LO expression. This represents a new mechanism by which leukotriene biosynthesis can be modulated by pathological agents | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Leukotrienes | |
| 650 | 4 | |a Mono Mac 1 | |
| 650 | 4 | |a Reporter gene assays | |
| 650 | 4 | |a TGF-β | |
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| 650 | 7 | |a Transforming Growth Factor beta1 |2 NLM | |
| 650 | 7 | |a Arachidonate 5-Lipoxygenase |2 NLM | |
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| 650 | 7 | |a ALOX5 protein, human |2 NLM | |
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| 700 | 1 | |a Boudreau, Luc H |e verfasserin |4 aut | |
| 700 | 1 | |a Flamand, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Surette, Marc E |e verfasserin |4 aut | |
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