Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells.
Recent evidence suggests the possibility that macrophages can influence lipoprotein metabolism. Therefore we investigated the ability of cultured macrophages to alter low density lipoprotein (LDL) uptake in a human liver cell line (HepG2). Conditioned media from phlogogenic-induced mouse peritoneal...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
1991-12-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520418929 |
| _version_ | 1818715731889487872 |
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| author | RI Grove C Mazzucco N Allegretto PA Kiener G Spitalny SF Radka M Shoyab M Antonaccio GA Warr |
| author_facet | RI Grove C Mazzucco N Allegretto PA Kiener G Spitalny SF Radka M Shoyab M Antonaccio GA Warr |
| author_sort | RI Grove |
| collection | DOAJ |
| description | Recent evidence suggests the possibility that macrophages can influence lipoprotein metabolism. Therefore we investigated the ability of cultured macrophages to alter low density lipoprotein (LDL) uptake in a human liver cell line (HepG2). Conditioned media from phlogogenic-induced mouse peritoneal macrophages or from a human macrophage cell line stimulated with endotoxin increased HepG2 LDL uptake by as much as 60-70%. The increase was due, in part, to a significant macrophage-induced 40% increase in the number of LDL receptors per cell. Although macrophage conditioned media inhibited HepG2 cholesterol synthesis, the LDL receptor up-regulation did not appear to be due to the effects on cholesterol synthesis. The LDL receptor stimulatory activity was sensitive to proteolysis and heat. Its molecular mass was approximately 20 kDa based on gel filtration. Several macrophage secretory proteins were tested in HepG2 cultures for LDL uptake stimulation. Of these, oncostatin M (approximately 18 kDa by gel filtration) gave the strongest response. The rank order for LDL uptake stimulation was oncostatin M much greater than interleukin 6 = interleukin 1 = transforming growth factor-beta 1. A neutralizing antibody directed against oncostatin M inhibited the ability of conditioned media to up-regulate LDL receptors by 85%. Thus, our results indicate that macrophages can secrete several proteins that up-regulate LDL receptors in HepG2 cells and that most of the up-regulatory activity in macrophage conditioned media appears to be due to oncostatin M. |
| first_indexed | 2024-12-17T19:08:02Z |
| format | Article |
| id | doaj.art-0c3b4b2925af4d1595f9300be38bbe32 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T19:08:02Z |
| publishDate | 1991-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-0c3b4b2925af4d1595f9300be38bbe322022-12-21T21:35:56ZengElsevierJournal of Lipid Research0022-22751991-12-01321218891897Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells.RI Grove0C Mazzucco1N Allegretto2PA Kiener3G Spitalny4SF Radka5M Shoyab6M Antonaccio7GA Warr8Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Oncogen, Bristol-Myers Squibb PRI, Seattle, WA 98121.Recent evidence suggests the possibility that macrophages can influence lipoprotein metabolism. Therefore we investigated the ability of cultured macrophages to alter low density lipoprotein (LDL) uptake in a human liver cell line (HepG2). Conditioned media from phlogogenic-induced mouse peritoneal macrophages or from a human macrophage cell line stimulated with endotoxin increased HepG2 LDL uptake by as much as 60-70%. The increase was due, in part, to a significant macrophage-induced 40% increase in the number of LDL receptors per cell. Although macrophage conditioned media inhibited HepG2 cholesterol synthesis, the LDL receptor up-regulation did not appear to be due to the effects on cholesterol synthesis. The LDL receptor stimulatory activity was sensitive to proteolysis and heat. Its molecular mass was approximately 20 kDa based on gel filtration. Several macrophage secretory proteins were tested in HepG2 cultures for LDL uptake stimulation. Of these, oncostatin M (approximately 18 kDa by gel filtration) gave the strongest response. The rank order for LDL uptake stimulation was oncostatin M much greater than interleukin 6 = interleukin 1 = transforming growth factor-beta 1. A neutralizing antibody directed against oncostatin M inhibited the ability of conditioned media to up-regulate LDL receptors by 85%. Thus, our results indicate that macrophages can secrete several proteins that up-regulate LDL receptors in HepG2 cells and that most of the up-regulatory activity in macrophage conditioned media appears to be due to oncostatin M.http://www.sciencedirect.com/science/article/pii/S0022227520418929 |
| spellingShingle | RI Grove C Mazzucco N Allegretto PA Kiener G Spitalny SF Radka M Shoyab M Antonaccio GA Warr Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. Journal of Lipid Research |
| title | Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. |
| title_full | Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. |
| title_fullStr | Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. |
| title_full_unstemmed | Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. |
| title_short | Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. |
| title_sort | macrophage derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520418929 |
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