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High glucose and interleukin-1beta downregulate interleukin-1 type I receptor (IL-1RI) in retinal endothelial cells by enhancing its degradation by a lysosome-dependent mechanism.

Authors: Aveleira, C  Castilho, A  Baptista, F  Simoes, N  Fernandes, C  Leal, E  Ambrosio, AF 
Citation: Aveleira C, etal., Cytokine. 2010 Mar;49(3):279-86. doi: 10.1016/j.cyto.2009.11.014. Epub 2010 Jan 19.
Pubmed: (View Article at PubMed) PMID:20034811
DOI: Full-text: DOI:10.1016/j.cyto.2009.11.014

Diabetic retinopathy has been considered a low-grade chronic inflammatory disease. The production of interleukin-1beta (IL-1beta) in the retina is increased, and this finding has been correlated with an increase in blood-retinal barrier permeability, suggesting that IL-1beta might have an important role in the pathogenesis of diabetic retinopathy. However, in this context, no attention has been given to interleukin-1 type I receptor (IL-1RI), which is the receptor responsible for IL-1beta triggered effects. Therefore, we investigated the effect of high glucose and IL-1beta on the IL-1RI regulation in retinal endothelial cells. A time-dependent downregulation of IL-1RI protein levels was detected in retinal endothelial cells exposed (1-24h) to high glucose, mannitol or IL-1beta. Long-term exposure (7days) to high glucose or mannitol also decreased IL-1RI protein content. IL-1RI downregulation was due to its activation by IL-1beta, since it was inhibited by the presence of anti-IL-1RI or anti-IL-1beta antibodies. Moreover, IL-1RI downregulation was prevented by lysosome inhibitors, chloroquine and ammonium chloride, but not by proteasome inhibitors, MG132 and lactacystin. We also found that IL-1RI translocates to the nucleus after high glucose or IL-1beta treatment. In conclusion, our results indicate that high glucose, probably due to osmotic stress, and IL-1beta downregulate IL-1RI in retinal endothelial cells. The downregulation of IL-1RI is triggered by its activation and is due, at least partially, to lysosomal degradation. High glucose and IL-1beta also enhance the translocation of IL-1RI to the nucleus.


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CRRD Object Information
CRRD ID: 7207030
Created: 2013-01-16
Species: All species
Last Modified: 2013-01-16
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.