Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase
Aims: Neutrophils can synthesize leukotriene B4 (LTB4) by activating the 5-lipoxygenase (5-LO)signaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hyper...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2014-11-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/366373 |
| _version_ | 1818479022162575360 |
|---|---|
| author | Xiao-Feng Lai Hua-Di Qin Lei-Lei Guo Zi-Guo Luo Jing Chang Chun-Chang Qin |
| author_facet | Xiao-Feng Lai Hua-Di Qin Lei-Lei Guo Zi-Guo Luo Jing Chang Chun-Chang Qin |
| author_sort | Xiao-Feng Lai |
| collection | DOAJ |
| description | Aims: Neutrophils can synthesize leukotriene B4 (LTB4) by activating the 5-lipoxygenase (5-LO)signaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2. |
| first_indexed | 2024-12-10T09:55:40Z |
| format | Article |
| id | doaj.art-050c465cf5ce4254998071d87f65bbdb |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T09:55:40Z |
| publishDate | 2014-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-050c465cf5ce4254998071d87f65bbdb2022-12-22T01:53:29ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-11-013451723173210.1159/000366373366373Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-LipoxygenaseXiao-Feng LaiHua-Di QinLei-Lei GuoZi-Guo LuoJing ChangChun-Chang QinAims: Neutrophils can synthesize leukotriene B4 (LTB4) by activating the 5-lipoxygenase (5-LO)signaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.http://www.karger.com/Article/FullText/3663735-LipoxygenaseLeukotriene B4Hypercholesterolemia |
| spellingShingle | Xiao-Feng Lai Hua-Di Qin Lei-Lei Guo Zi-Guo Luo Jing Chang Chun-Chang Qin Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase Cellular Physiology and Biochemistry 5-Lipoxygenase Leukotriene B4 Hypercholesterolemia |
| title | Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase |
| title_full | Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase |
| title_fullStr | Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase |
| title_full_unstemmed | Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase |
| title_short | Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase |
| title_sort | hypercholesterolemia increases the production of leukotriene b4 in neutrophils by enhancing the nuclear localization of 5 lipoxygenase |
| topic | 5-Lipoxygenase Leukotriene B4 Hypercholesterolemia |
| url | http://www.karger.com/Article/FullText/366373 |
| work_keys_str_mv | AT xiaofenglai hypercholesterolemiaincreasestheproductionofleukotrieneb4inneutrophilsbyenhancingthenuclearlocalizationof5lipoxygenase AT huadiqin hypercholesterolemiaincreasestheproductionofleukotrieneb4inneutrophilsbyenhancingthenuclearlocalizationof5lipoxygenase AT leileiguo hypercholesterolemiaincreasestheproductionofleukotrieneb4inneutrophilsbyenhancingthenuclearlocalizationof5lipoxygenase AT ziguoluo hypercholesterolemiaincreasestheproductionofleukotrieneb4inneutrophilsbyenhancingthenuclearlocalizationof5lipoxygenase AT jingchang hypercholesterolemiaincreasestheproductionofleukotrieneb4inneutrophilsbyenhancingthenuclearlocalizationof5lipoxygenase AT chunchangqin hypercholesterolemiaincreasestheproductionofleukotrieneb4inneutrophilsbyenhancingthenuclearlocalizationof5lipoxygenase |