Synthesis and secretion of tumour necrosis factor-α by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts

Abordo, Evelyn A.; Thornalley, Paul J.

doi:10.1016/s0165-2478(97)00080-1

Cited by 55 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3, is that these AGE precursors diffuse out of the cell and modify circulating proteins in the blood such as albumin. These modified circulating proteins can then bind to AGE receptors and activate them, thereby causing the production of inflammatory cytokines and growth factors, which in turn cause vascular pathology (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Again, how do we know that this piece of the puzzle is really important?…”

Section: Pieces Of the Puzzlementioning

confidence: 99%

The Pathobiology of Diabetic Complications

2005

View full text Add to dashboard Cite

Section: Pieces Of the Puzzlementioning

confidence: 99%

The Pathobiology of Diabetic Complications

2005

View full text Add to dashboard Cite

“…GTS-21 significantly attenuated TNF production by 62% in monocytes stimulated with HMGB1. Advanced glycation end products (AGEs), proteins modified by glycosylation and oxidation via nonenzymatic processes, occur as a consequence of protracted hyperglycemia, and activate monocytes by binding to RAGE (26,27). GTS-21 significantly reduced TNF levels by 80% in monocytes activated by exposure to AGE-modified albumin (Figure 4).…”

Section: Gts-21 Attenuates Production Of Tnf By Monocytes Stimulated mentioning

confidence: 99%

“…AGEs are molecules modified by glycosylation and oxidation via nonenzymatic processes occurring in environments of oxidative stress and hyperglycemia. AGEs signal through RAGE receptors and induce proinflammatory cytokine production by macrophages and monocytes (26,27). AGEs have been implicated in the pathogenesis of vascular complication of diabetes (45) and Alzheimer's disease (46).…”

Section: R E S E a R C H A R T I C L Ementioning

confidence: 99%

The Selective α7 Agonist GTS-21 Attenuates Cytokine Production in Human Whole Blood and Human Monocytes Activated by Ligands for TLR2, TLR3, TLR4, TLR9, and RAGE

Rosas-Ballina

Goldstein

Gallowitsch-Puerta

et al. 2009

Mol Med

184

101

View full text Add to dashboard Cite

“…30,31 Because this cytokine stimulates LOX-1 expression in vascular cells 13,17 and is released by monocytic cells in response to high glucose and AGE, [32][33][34][35] we determined the modulatory effect of TNF-␣ on human MDM LOX-1 expression under normal and high glucose conditions. As shown in Figures 3A and 3B, TNF-␣-treated human MDMs cultured under normoglycemic conditions express similar levels of LOX-1 gene and protein expression as high glucose-treated cells.…”

Section: Effect Of High Glucose On Tumor Necrosis Factor-␣-induced MDmentioning

confidence: 99%

Glucose Enhances Human Macrophage LOX-1 Expression

Sawamura

Renier

2004

Circulation Research

145

View full text Add to dashboard Cite

Abstract-Lectin-like oxidized LDL receptor-1 (LOX-1) is a newly identified receptor for oxidized LDL that is expressed by vascular cells. LOX-1 is upregulated in aortas of diabetic rats and thus may contribute to the pathogenesis of human diabetic atherosclerosis. In this study, we examined the regulation of human monocyte-derived macrophage (MDM) LOX-1 expression by high glucose and the role of LOX-1 in glucose-induced foam cell formation. Incubation of human MDMs with glucose (5.6 to 30 mmol/L) enhanced, in a dose-and time-dependent manner, LOX-1 gene and protein expression. Induction of LOX-1 gene expression by high glucose was abolished by antioxidants, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), nuclear factor-B (NF-B), and activated protein-1 (AP-1) inhibitors. In human MDMs cultured with high glucose, increased expression of PKC␤ 2 and enhanced phosphorylation of extracellular signal-regulated protein kinase 1/2 was observed. Activation of these kinases was inhibited by the antioxidant N-acetyl-L-cysteine (NAC) and by the PKC␤ inhibitor LY379196. High glucose also enhanced the binding of nuclear proteins extracted from human MDMs to the NF-B and AP-1 regulatory elements of the LOX-1 gene promoter. This effect was abrogated by NAC and PKC/MAPK inhibitors. Finally, high glucose induced human macrophage-derived foam cell formation through a LOX-1-dependent pathway. Overall, these results demonstrate that high glucose concentrations enhance LOX-1 expression in human MDMs and that this effect is associated with foam cell formation. Pilot data showing that MDMs of patients with type 2 diabetes overexpress LOX-1 support the relevance of this work to human diabetic atherosclerosis. Key Words: macrophages Ⅲ lectin-like oxidized low-density lipoprotein receptor-1 Ⅲ glucose Ⅲ diabetes Ⅲ foam cell formation T he prevalence, incidence, and mortality from all forms of cardiovascular diseases are increased in patients with diabetes. 1 Among the cardiovascular risk factors documented in diabetes, hyperglycemia appears as an independent risk factor for diabetic macrovascular complications. 2 Mechanisms through which hyperglycemia may promote the development of diabetic cardiovascular disease include glycoxidation and lipoxidation, increased oxidative stress, and protein kinase C (PKC) activation. [3][4][5][6][7][8] One of the earliest events in atherogenesis is the accumulation of oxidized LDL (oxLDL) in the intima and the subsequent uptake of this modified lipoprotein by macrophages, leading to foam cell formation. 9 One limiting factor for oxLDL uptake by endothelial cells is lectin-like oxLDL receptor-1 (LOX-1), a newly identified vascular receptor for oxLDL. 10 -12 Accumulating evidence indicates a key role for LOX-1 in atherogenesis. First, uptake of oxLDL by endothelial cells through LOX-1 induces endothelial dysfunction. Second, the two main LOX-1 ligands, oxLDL and advanced glycation end products (AGE), are implicated in the pathogenesis of atherosclerosis. 5,9 Third, expression of LOX-1 b...

show abstract

Synthesis and secretion of tumour necrosis factor-α by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts

Cited by 55 publications

References 45 publications

The Pathobiology of Diabetic Complications

The Pathobiology of Diabetic Complications

The Selective α7 Agonist GTS-21 Attenuates Cytokine Production in Human Whole Blood and Human Monocytes Activated by Ligands for TLR2, TLR3, TLR4, TLR9, and RAGE

Glucose Enhances Human Macrophage LOX-1 Expression

Contact Info

Product

Resources

About