High Glucose-Induced Expression of Proinflammatory Cytokine and Chemokine Genes in Monocytic Cells
Reads0
Chats0
TLDR
Results show for the first time that multiple inflammatory cytokines and chemokines relevant to the pathogenesis of diabetes complications are induced by HG via key signaling pathways.Abstract:
Monocyte activation and adhesion to the endothelium play important roles in inflammatory and cardiovascular diseases. These processes are further aggravated by hyperglycemia, leading to cardiovascular complications in diabetes. We have previously shown that high glucose (HG) treatment activates monocytes and induces the expression of tumor necrosis factor (TNF)-α via oxidant stress and nuclear factor-kB transcription factor. To determine the effects of HG on the expression of other inflammatory genes, in the present study, HG-induced gene profiling was performed in THP-1 monocytes using cytokine gene arrays containing 375 known genes. HG treatment upregulated the expression of 41 genes and downregulated 15 genes that included chemokines, cytokines, chemokines receptors, adhesion molecules, and integrins. RT-PCR analysis further confirmed that HG significantly increased the expression of monocyte chemoattractant protein-1 (MCP-1), TNF-α, β 2 -integrin, interleukin-1β, and others. HG treatment increased transcription of the MCP-1 gene, MCP-1 protein levels, and adhesion of THP-1 cells to endothelial cells. HG-induced MCP-1 mRNA expression and monocyte adhesion were blocked by specific inhibitors of oxidant stress, protein kinase C, ERK1/2, and p38 mitogen-activated protein kinases. These results show for the first time that multiple inflammatory cytokines and chemokines relevant to the pathogenesis of diabetes complications are induced by HG via key signaling pathways.read more
Citations
More filters
Journal ArticleDOI
Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?
Iciar Martín-Timón,Cristina Sevillano-Collantes,Amparo Segura-Galindo,Francisco Javier del Cañizo-Gómez +3 more
TL;DR: In this article, the authors highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.
Journal ArticleDOI
Epigenetics: A Molecular Link Between Environmental Factors and Type 2 Diabetes
Charlotte Ling,Leif Groop +1 more
TL;DR: A perspective will focus on the roles of DNA methylation and histone modification in the pathogenesis of type 2 diabetes, suggesting a role for epigenetic factors in the complex interplay between genes and the environment.
Journal ArticleDOI
Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises.
TL;DR: DKA and NKH are associated with elevation of proinflammatory cytokines, ROS, and cardiovascular risk factors in the absence of obvious infection or cardiovascular pathology, and return of these values to normal levels with insulin therapy demonstrates a robust anti-inflammatory effect of insulin.
Journal ArticleDOI
An immune origin of type 2 diabetes
TL;DR: Subclinical, low-grade systemic inflammation has been observed in patients with type 2 diabetes and in those at increased risk of the disease, and targeting of immune genes enhanced or suppressed the development of obesity or diabetes in animal models is suggested.
Journal ArticleDOI
High glucose induces Toll-like receptor expression in human monocytes: Mechanism of activation
TL;DR: It is suggested that high glucose induces TLR2 and -4 expression via PKC-α and PKc-δ, respectively, by stimulating NADPH oxidase in human monocytes by stimulating the expression and activity of TLRs in hyperglycemic conditions.
References
More filters
Journal ArticleDOI
Role of Oxidative Stress in Development of Complications in Diabetes
TL;DR: Structural characterization of the cross-links and other products accumulating in collagen in diabetes is needed to gain a better understanding of the relationship between oxidative stress and the development of complications in diabetes.
superoxide production blocks three pathways of hyperglycaemic damage
Takeshi Nishikawa,Diane Edelstein,Xue Liang Du,Sho-ichi Yamagishi,Takeshi Matsumura,Yasufumi Kaneda,Mark A. Yorek,David Beebek,Peter J. Oatesk,Hans-Peter Hammes,Ida Giardino,Michael Brownlee +11 more
TL;DR: This paper showed that hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells and that this increase in reactive oxygen can be prevented by an inhibitor of electron transport chain complex II, an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase.
Journal ArticleDOI
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Takeshi Nishikawa,Diane Edelstein,Xue Liang Du,Sho-ichi Yamagishi,Takeshi Matsumura,Yasufumi Kaneda,Mark A. Yorek,David A. Beebe,Peter J. Oates,Hans-Peter Hammes,Ida Giardino,Michael Brownlee +11 more
TL;DR: This work shows that hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells and is prevented by an inhibitor of electron transport chain complex II, by an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase.
Journal ArticleDOI
Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications.
TL;DR: This seminar reviews recent studies suggesting that the central pathologic features of diabetic complications are caused by the hyperglycemia-accelerated formation of nonenzymatic advanced gly...
Journal ArticleDOI
Role of oxidative stress in diabetic complications: a new perspective on an old paradigm.
John W. Baynes,S R Thorpe +1 more
TL;DR: In this article, the authors investigated whether increased oxidative stress has a primary role in the pathogenesis of diabetic complications or whether it is a secondary indicator of end-stage tissue damage in diabetes.