Role of interleukin-1beta in the pathogenesis of diabetic retinopathy.
OBJECTIVE
To examine the role of cytokine interleukin-1beta (IL-1beta) in retinal capillary cell death in diabetes.


METHODS
The effect of glucose on the expression of IL-1beta was measured in the bovine retinal endothelial cells. The role of IL-1beta in the accelerated endothelial cell loss was determined by investigating the effect of human recombinant IL-1beta on their apoptosis in normal and high glucose conditions, and was confirmed using interleukin-1 receptor antagonist (IL-1ra).


RESULTS
High glucose increased IL-1beta expression by 60% compared with cells incubated in 5 mM glucose (p<0.05). Incubation of cells with IL-1beta increased NO levels by about 80% and activated NF-kappaB by 40%. In the same cells apoptosis was increased by 70% and caspase-3 activity was increased by 40%. Supplementation of IL-1beta in 20 mM glucose medium further increased nitric oxide and NF-kappaB, and accelerated apoptosis, and addition of IL-1ra significantly decreased glucose induced abnormalities and apoptosis.


CONCLUSIONS
IL-1beta accelerates apoptosis of retinal capillary cells via activation of NF-kappaB, and the process is exacerbated in high glucose conditions. These studies suggest a possible role of IL-1beta in the development of retinopathy in diabetes, and offer a possible rationale to test IL-1beta receptor antagonists to inhibit the development of diabetic retinopathy.
Kowluru
R A
RA
Kresge Eye Institute, Wayne State University, Detroit, MI 48201, USA. rkowluru@med.wayne.edu
Odenbach
S
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism
D007375:Interleukin-1; D011994:Recombinant Proteins; D009569:Nitric Oxide; D005947:Glucose