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Aveleira C.,Institute of Biomedical Research in Light and Image IBILI | Castilho A.,Institute of Biomedical Research in Light and Image IBILI | Baptista F.,Institute of Biomedical Research in Light and Image IBILI | Simoes N.,Institute of Biomedical Research in Light and Image IBILI | And 5 more authors.
Cytokine | Year: 2010

Diabetic retinopathy has been considered a low-grade chronic inflammatory disease. The production of interleukin-1β (IL-1β) in the retina is increased, and this finding has been correlated with an increase in blood-retinal barrier permeability, suggesting that IL-1β 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-1β triggered effects. Therefore, we investigated the effect of high glucose and IL-1β 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 (1-24 h) to high glucose, mannitol or IL-1β. Long-term exposure (7 days) to high glucose or mannitol also decreased IL-1RI protein content. IL-1RI downregulation was due to its activation by IL-1β, since it was inhibited by the presence of anti-IL-1RI or anti-IL-1β 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-1β treatment. In conclusion, our results indicate that high glucose, probably due to osmotic stress, and IL-1β 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-1β also enhance the translocation of IL-1RI to the nucleus. © 2009 Elsevier Ltd. All rights reserved.

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