Back to Search
Start Over
High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity
- Source :
- Atherosclerosis. 202:363-371
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Recent diabetes control and complications trial and epidemiology of diabetes interventions and complications (DCCT/EDIC) and other clinical studies have reported that glucose control in patients with diabetes leads to a significant reduction of cardiovascular events and atherosclerosis, indicating that hyperglycemia plays an essential role in cardiovascular disease in diabetic patients. Although several mechanisms by which hyperglycemia promotes atherosclerosis have been proposed, it remains unclear how hyperglycemia promotes atherosclerosis by interaction with inflammatory cytokines. To test our hypothesis that hyperglycemia interplays with interferon gamma (IFN gamma), a key factor involved in atherosclerosis, to up-regulate the expression of genes such as matrix metalloproteinases (MMPs) and cytokines that are involved in plaque destabilization, U937 macrophages cultured in medium containing either normal or high glucose were challenged with IFN gamma and the expression of MMPs and cytokines were then quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results showed that high glucose and IFN gamma had a synergistic effect on the expression of MMP-1, MMP-9 and IL-1 beta. High glucose also enhanced IFN gamma-induced priming effect on lipopolysaccharide (LPS)-stimulated MMP-1 secretion. Furthermore, high glucose and IFN gamma exert the synergistic effect on MMP-1 expression by enhancing STAT1 phosphorylation and STAT1 transcriptional activity. In summary, this study revealed a novel mechanism potentially involved in diabetes-promoted cardiovascular disease.
- Subjects :
- medicine.medical_specialty
Lipopolysaccharide
Interleukin-1beta
Inflammation
Article
Proinflammatory cytokine
Interferon-gamma
chemistry.chemical_compound
Diabetes mellitus
Internal medicine
medicine
Humans
Macrophage
Interferon gamma
STAT1
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
biology
U937 cell
Macrophages
JNK Mitogen-Activated Protein Kinases
Drug Synergism
U937 Cells
Atherosclerosis
medicine.disease
Glucose
STAT1 Transcription Factor
Endocrinology
Matrix Metalloproteinase 9
chemistry
Hyperglycemia
biology.protein
Matrix Metalloproteinase 1
medicine.symptom
Cardiology and Cardiovascular Medicine
Diabetic Angiopathies
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 00219150
- Volume :
- 202
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....3ea62ab6aa22fb9dbd5196c766bc595a