Journal
DIABETES
Volume 53, Issue 3, Pages 795-802Publisher
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.53.3.795
Keywords
-
Categories
Funding
- NCRR NIH HHS [MO1RR00043] Funding Source: Medline
- NHLBI NIH HHS [P01 HL55798] Funding Source: Medline
- NIDDK NIH HHS [R01 DK58191, R01 DK065073] Funding Source: Medline
Ask authors/readers for more resources
The cyclooxygenase (COX)-2 enzyme has been implicated in the pathogenesis of several inflammatory diseases. However, its role in diabetic vascular disease is unclear. In this study, we evaluated the hypothesis that diabetic conditions can induce COX-2 in monocytes. High glucose treatment of THP-1 monocytic cells led to a significant three- to fivefold induction of COX-2 mRNA and protein expression but not COX-I mRNA. High glucose-induced COX-2 mRNA was blocked by inhibitors of nuclear factor-kappaB (NF-kappaB), protein kinase C, and p38 mitogen-activated protein kinase. In addition, an antioxidant and inhibitors of mitochondrial superoxide, NADPH oxidase, and glucose metabolism to glucosamine also blocked high glucose-induced COX-2 expression to varying degrees. High glucose significantly increased transcription from a human COX-2 promoter-luciferase construct (twofold, P<0.001). Promoter deletion analyses and inhibition of transcription by NF-kappa B superrepressor and cAMP-responsive element binding (CREB) mutants confirmed the involvement of NF-kappa B and CREB transcription factors in high glucose-induced COX-2 regulation. In addition, isolated peripheral blood monocytes from type 1 and type 2 diabetic patients had high levels of COX-2 mRNA, whereas those from normal volunteers showed no expression. These results show that high glucose and diabetes can augment inflammatory responses by upregulating COX-2 via multiple signaling pathways, leading to monocyte activation relevant to the pathogenesis of diabetes complications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available