Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells

Samar M. Hammad, Waleed O. Twal, Jeremy L. Barth, Kent J. Smith, Antonio Saad, Gabriel Virella, W. Scott Argraves, Maria F. Lopes-Virella

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 4 h. 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-κB /NF-κB 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-β 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 Fcγ 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.

Original languageEnglish (US)
Pages (from-to)394-404
Number of pages11
JournalAtherosclerosis
Volume202
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Fingerprint

U937 Cells
Antigen-Antibody Complex
Inflammation
Gene Expression
Survival
Genes
oxidized low density lipoprotein
Unfolded Protein Response
Fc Receptors
Gene Expression Profiling
Endocytosis
Oligonucleotide Array Sequence Analysis
Cell Survival
Atherosclerosis
Carrier Proteins
Oxidoreductases

Keywords

  • Atherosclerosis
  • DNA microarray
  • Fc gamma receptors
  • Oxidized LDL
  • Oxidized LDL immune complexes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. / Hammad, Samar M.; Twal, Waleed O.; Barth, Jeremy L.; Smith, Kent J.; Saad, Antonio; Virella, Gabriel; Argraves, W. Scott; Lopes-Virella, Maria F.

In: Atherosclerosis, Vol. 202, No. 2, 01.02.2009, p. 394-404.

Research output: Contribution to journalArticle

Hammad, Samar M. ; Twal, Waleed O. ; Barth, Jeremy L. ; Smith, Kent J. ; Saad, Antonio ; Virella, Gabriel ; Argraves, W. Scott ; Lopes-Virella, Maria F. / Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. In: Atherosclerosis. 2009 ; Vol. 202, No. 2. pp. 394-404.
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AU - Twal, Waleed O.

AU - Barth, Jeremy L.

AU - Smith, Kent J.

AU - Saad, Antonio

AU - Virella, Gabriel

AU - Argraves, W. Scott

AU - Lopes-Virella, Maria F.

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