AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-κB pathways

Liu, YaYang; Liang, Chieh Kai; Liu, Xing; Liao, Bin; Pan, Xiaoming; Ren, Yusheng; Fan, Min; Mei, Li; He, Zhiqing; Wu, Ji; Wu, Zonggui

doi:10.1016/j.atherosclerosis.2009.06.007

Cited by 91 publications

(70 citation statements)

References 37 publications

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“…The effects of AGEs are thought to be mediated through specific binding to RAGE since the neutralization of RAGE on several types of cells can block those effects [21,22]. We also performed blocking experiments by culturing basophils with glycated albumin at 1 mg/ml plus anti-RAGE mAb at 20 µg/ml.…”

Section: Discussionmentioning

confidence: 99%

The in vitro Effects of Advanced Glycation End Products on Basophil Functions

Han

Suzukawa²,

Yamaguchi³

et al. 2011

Int Arch Allergy Immunol

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Background: Basophils are thought to play pivotal roles in the pathogenesis of allergic reactions, but their roles in inflammation associated with systemic abnormalities such as metabolic disorders remain largely unknown. Advanced glycation end products (AGEs) are potentially important substances produced in high-glucose disease conditions. In this in vitro study, we investigated whether the biological functions of human basophils can be influenced by AGEs. Methods: We analyzed the effects of AGEs on various functions and markers of human basophils, including CD11b expression, apoptosis, degranulation, and cytokine production. Results: Flow cytometric analysis indicated that the level of the receptor for AGEs (RAGE) on the surface of freshly isolated basophils was very low but was clearly upregulated by IL-3. Apoptosis of basophils was induced by high concentrations of glycated albumin. Although glycated albumin failed to affect the level of surface CD11b expression or to trigger degranulation or production of IL-4 and IL-13 in basophils, it dose-dependently induced IL-6 and IL-8 secretion. Conclusions: AGEs seem to act on human basophils; they suppress the cells’ longevity but elicit secretion of inflammatory cytokines. Through these biological changes, basophils might play some roles in inflammatory conditions associated with metabolic disorders presenting elevated levels of AGEs.

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Section: Discussionmentioning

confidence: 99%

The in vitro Effects of Advanced Glycation End Products on Basophil Functions

Han

Suzukawa²,

Yamaguchi³

et al. 2011

Int Arch Allergy Immunol

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“…Blockade of S100B-induced MCP-1 expression by inhibitors of MEK1 and p38, as shown in this study, is consistent with previous studies showing that both ERK1/2 and p38 are involved in RAGE-mediated NF-B activation and subsequent MCP-1 expression in VSMC 21,36) . Although several previous studies have shown that JNK is one of the signaling pathways downstream of RAGE in endothelial cells 8) and adventitia fibroblasts 37) , the present study, to the best of our knowledge, demonstrated for the first time the role of JNK in the RAGEmediated response in VSMC. These results suggest that JNK as well as ERK1/2 and p38 plays a pivotal role in the development and/or progression of RAGEinduced vascular lesions.…”

Section: Discussionmentioning

confidence: 62%

Overexpression of Receptor for Advanced Glycation End Products Induces Monocyte Chemoattractant Protein-1 Expression in Rat Vascular Smooth Muscle Cell Line

Hayakawa

Yoshimoto

Sekizawa

et al. 2012

JAT

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Aim:The receptor for advanced glycation end-products (RAGE) has been suggested to play a pivotal role in the development of diabetic vasculopathy and atherosclerosis; however, due to its low expression, the physiological role of RAGE in vascular smooth muscle cells (VSMC) remains unknown. Methods: Using VSMC lines stably expressing RAGE (RAGE-A10), we studied the molecular mechanism by which S100B, a RAGE ligand, induces proinflammatory gene expression. Results: S100B induced NF-B activation and the expression of several proinflammatory genes (MCP-1, IL-6, ICAM-1) at mRNA and protein levels in RAGE-A10, among which MCP-1 expression was the most robust. S100B-induced MCP-1 expression was dose-dependently blocked by inhibitors of JNK (SP600125), p38 (SB203580), MEK-1 (U0126) as well as NF-B (Bay117085). In RAGE-A10, S100B activated JNK, MEK-1 and p38. S100B-induced MCP-1 promoter activity via NF-B binding sites and nuclear translocation of NF-B p65 subunit were blocked by SP600125, U0126, and SB203580 in RAGE-A10. Conclusion: Our study demonstrates that S100B increased MCP-1 expression via NF-B and mitogen-activated protein kinase (JNK, ERK1/2, and p38) pathways in RAGE-overexpressed A10 cell lines. Thus, RAGE-A10 could be a useful cell model for studying the molecular mechanism(s) of upregulated RAGE in the vasculature. J Atheroscler Thromb, 2012; 19:13-22.

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“…In vitro, diabetes appears to enhance vascular smooth muscle cell proliferation and migration through alterations in proteases, integrins, glycoproteins and formation of Advanced Glycation Endproducts (AGEs) (20,21). In vivo, elevated blood glucose levels have been shown to induce a series of alterations within the vasculature including endothelial dysfunction, cellular proliferation, changes in extracellular matrix conformation and impairment of LDL receptor-mediated uptake decreasing the in vivo clearance of LDL concentrations (22)(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%