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IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation.
PLoS One. 2012; 7(5):e36949.Plos

Abstract

Many molecular and cellular abnormalities detected in the diabetic retina support a role for IL-1β-driven neuroinflammation in the pathogenesis of diabetic retinopathy. IL-1β is well known for its role in the induction and, through autostimulation, amplification of neuroinflammation. Upregulation of IL-1β has been consistently detected in the diabetic retina; however, the mechanisms and cellular source of IL-1β overexpression are poorly understood. The aim of this study was to investigate the effect of high glucose and IL-1β itself on IL-1β expression in microglial, macroglial (astrocytes and Müller cells) and retinal vascular endothelial cells; and to study the effect of diabetes on the expression of IL-1β in isolated retinal vessels and on the temporal pattern of IL-1β upregulation and glial reactivity in the retina of streptozotocin-diabetic rats. IL-1β was quantified by RealTime RT-PCR and ELISA, glial fibrillar acidic protein, α2-macroglobulin, and ceruloplasmin by immunoblotting. We found that high glucose induced a 3-fold increase of IL-1β expression in retinal endothelial cells but not in macroglia and microglia. IL-1β induced its own synthesis in endothelial and macroglial cells but not in microglia. In retinal endothelial cells, the high glucose-induced IL-1β overexpression was prevented by calphostin C, a protein kinase C inhibitor. The retinal vessels of diabetic rats showed increased IL-1β expression as compared to non-diabetic rats. Retinal expression of IL-1β increased early after the induction of diabetes, continued to increase with progression of the disease, and was temporally associated with upregulation of markers of glial activation. These findings point to hyperglycemia as the trigger and to the endothelium as the origin of the initial retinal upregulation of IL-1β in diabetes; and to IL-1β itself, via autostimulation in endothelial and macroglial cells, as the mechanism of sustained IL-1β overexpression. Interrupting the vicious circle triggered by IL-1β autostimulation could limit the progression of diabetic retinopathy.

Authors+Show Affiliations

Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22615852

Citation

Liu, Yang, et al. "IL-1β Is Upregulated in the Diabetic Retina and Retinal Vessels: Cell-specific Effect of High Glucose and IL-1β Autostimulation." PloS One, vol. 7, no. 5, 2012, pp. e36949.
Liu Y, Biarnés Costa M, Gerhardinger C. IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation. PLoS One. 2012;7(5):e36949.
Liu, Y., Biarnés Costa, M., & Gerhardinger, C. (2012). IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation. PloS One, 7(5), e36949. https://doi.org/10.1371/journal.pone.0036949
Liu Y, Biarnés Costa M, Gerhardinger C. IL-1β Is Upregulated in the Diabetic Retina and Retinal Vessels: Cell-specific Effect of High Glucose and IL-1β Autostimulation. PLoS One. 2012;7(5):e36949. PubMed PMID: 22615852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation. AU - Liu,Yang, AU - Biarnés Costa,Montserrat, AU - Gerhardinger,Chiara, Y1 - 2012/05/16/ PY - 2011/11/03/received PY - 2012/04/16/accepted PY - 2012/5/23/entrez PY - 2012/5/23/pubmed PY - 2013/1/9/medline SP - e36949 EP - e36949 JF - PloS one JO - PLoS One VL - 7 IS - 5 N2 - Many molecular and cellular abnormalities detected in the diabetic retina support a role for IL-1β-driven neuroinflammation in the pathogenesis of diabetic retinopathy. IL-1β is well known for its role in the induction and, through autostimulation, amplification of neuroinflammation. Upregulation of IL-1β has been consistently detected in the diabetic retina; however, the mechanisms and cellular source of IL-1β overexpression are poorly understood. The aim of this study was to investigate the effect of high glucose and IL-1β itself on IL-1β expression in microglial, macroglial (astrocytes and Müller cells) and retinal vascular endothelial cells; and to study the effect of diabetes on the expression of IL-1β in isolated retinal vessels and on the temporal pattern of IL-1β upregulation and glial reactivity in the retina of streptozotocin-diabetic rats. IL-1β was quantified by RealTime RT-PCR and ELISA, glial fibrillar acidic protein, α2-macroglobulin, and ceruloplasmin by immunoblotting. We found that high glucose induced a 3-fold increase of IL-1β expression in retinal endothelial cells but not in macroglia and microglia. IL-1β induced its own synthesis in endothelial and macroglial cells but not in microglia. In retinal endothelial cells, the high glucose-induced IL-1β overexpression was prevented by calphostin C, a protein kinase C inhibitor. The retinal vessels of diabetic rats showed increased IL-1β expression as compared to non-diabetic rats. Retinal expression of IL-1β increased early after the induction of diabetes, continued to increase with progression of the disease, and was temporally associated with upregulation of markers of glial activation. These findings point to hyperglycemia as the trigger and to the endothelium as the origin of the initial retinal upregulation of IL-1β in diabetes; and to IL-1β itself, via autostimulation in endothelial and macroglial cells, as the mechanism of sustained IL-1β overexpression. Interrupting the vicious circle triggered by IL-1β autostimulation could limit the progression of diabetic retinopathy. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22615852/IL_1β_is_upregulated_in_the_diabetic_retina_and_retinal_vessels:_cell_specific_effect_of_high_glucose_and_IL_1β_autostimulation_ L2 - https://dx.plos.org/10.1371/journal.pone.0036949 DB - PRIME DP - Unbound Medicine ER -