Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells
OBJECTIVE: To compare the global effects of oxidized LDL (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) on gene expression in human monocytic cells and to identify differentially expressed genes involved with inflammation and survival.
METHODS AND RESULTS: U937 cells were treated with oxLDL-IC, oxLDL, Keyhole limpet hemocyanin immune complexes (KLH-IC), or vehicle for 4h. Transcriptome profiling was performed using DNA microarrays. oxLDL-IC uniquely affected the expression of genes involved with pro-survival (RAD54B, RUFY3, SNRPB2, and ZBTB24). oxLDL-IC also regulated many genes in a manner similar to KLH-IC. Functional categorization of these genes revealed that 39% are involved with stress responses, including the unfolded protein response which impacts cell survival, 19% with regulation of transcription, 10% with endocytosis and intracellular transport of protein and lipid, and 16% with inflammatory responses including regulation of I-kappaB /NF-kappaB cascade and cytokine activity. One gene in particular, HSPA6, greatly up-regulated by oxLDL-IC, was found to be required for the process by which oxLDL-IC augments IL1-beta secretion. The study also revealed genes uniquely up-regulated by oxLDL, including genes involved with growth inhibition (OKL38, NEK3, and FTH1), oxidoreductase activity (SPXN1 and HMOX1), and transport of amino acids and fatty acids (SLC7A11 and ADFP).
CONCLUSIONS: These findings highlight early transcriptional responses elicited by oxLDL-IC that may underlie its cytoprotective and pro-inflammatory effects. Cross-linking of Fc gamma receptors appears to be the trigger for most of the transcriptional responses to oxLDL-IC. The findings further strengthen the hypothesis that oxLDL and oxLDL-IC elicit disparate inflammatory responses and play distinct roles in the process of atherosclerosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:202 |
|---|---|
| Enthalten in: |
Atherosclerosis - 202(2009), 2 vom: 20. Feb., Seite 394-404 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hammad, Samar M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.04.2009 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.atherosclerosis.2008.05.032 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM180628100 |
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| 041 | |a eng | ||
| 100 | 1 | |a Hammad, Samar M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 08.04.2009 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To compare the global effects of oxidized LDL (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) on gene expression in human monocytic cells and to identify differentially expressed genes involved with inflammation and survival | ||
| 520 | |a METHODS AND RESULTS: U937 cells were treated with oxLDL-IC, oxLDL, Keyhole limpet hemocyanin immune complexes (KLH-IC), or vehicle for 4h. Transcriptome profiling was performed using DNA microarrays. oxLDL-IC uniquely affected the expression of genes involved with pro-survival (RAD54B, RUFY3, SNRPB2, and ZBTB24). oxLDL-IC also regulated many genes in a manner similar to KLH-IC. Functional categorization of these genes revealed that 39% are involved with stress responses, including the unfolded protein response which impacts cell survival, 19% with regulation of transcription, 10% with endocytosis and intracellular transport of protein and lipid, and 16% with inflammatory responses including regulation of I-kappaB /NF-kappaB cascade and cytokine activity. One gene in particular, HSPA6, greatly up-regulated by oxLDL-IC, was found to be required for the process by which oxLDL-IC augments IL1-beta secretion. The study also revealed genes uniquely up-regulated by oxLDL, including genes involved with growth inhibition (OKL38, NEK3, and FTH1), oxidoreductase activity (SPXN1 and HMOX1), and transport of amino acids and fatty acids (SLC7A11 and ADFP) | ||
| 520 | |a CONCLUSIONS: These findings highlight early transcriptional responses elicited by oxLDL-IC that may underlie its cytoprotective and pro-inflammatory effects. Cross-linking of Fc gamma receptors appears to be the trigger for most of the transcriptional responses to oxLDL-IC. The findings further strengthen the hypothesis that oxLDL and oxLDL-IC elicit disparate inflammatory responses and play distinct roles in the process of atherosclerosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Antigen-Antibody Complex |2 NLM | |
| 650 | 7 | |a Lipoproteins, LDL |2 NLM | |
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| 650 | 7 | |a oxidized low density lipoprotein |2 NLM | |
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| 700 | 1 | |a Twal, Waleed O |e verfasserin |4 aut | |
| 700 | 1 | |a Barth, Jeremy L |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Kent J |e verfasserin |4 aut | |
| 700 | 1 | |a Saad, Antonio F |e verfasserin |4 aut | |
| 700 | 1 | |a Virella, Gabriel |e verfasserin |4 aut | |
| 700 | 1 | |a Argraves, W Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes-Virella, Maria F |e verfasserin |4 aut | |
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