June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Impact of Interleukin-1α on Hyperglycemia-Induced Inflammation and Cell Death in Müller Cells
Author Affiliations & Notes
  • Derrick Feenstra
    Physiology, Michigan State University, East Lansing, MI
  • Prathiba Jayaguru
    Physiology, Michigan State University, East Lansing, MI
  • Charles Dinarello
    Division of Infectious Diseases, University of Colorado Denver, Aurora, CO
  • Susanne Mohr
    Physiology, Michigan State University, East Lansing, MI
  • Footnotes
    Commercial Relationships Derrick Feenstra, None; Prathiba Jayaguru, None; Charles Dinarello, None; Susanne Mohr, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3243. doi:
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      Derrick Feenstra, Prathiba Jayaguru, Charles Dinarello, Susanne Mohr; Impact of Interleukin-1α on Hyperglycemia-Induced Inflammation and Cell Death in Müller Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3243.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Inflammation mediated by interleukin-1β (IL-1β)/IL-1 receptor plays a key role in the progression of diabetic retinopathy. Müller cells are the main source of IL-1β contributing to retinal inflammation in diabetes. Whereas much is known about the activation of IL-1β signaling, less is known about interleukin-1α (IL-1α), which activates the same IL-1 receptor and possesses the same inflammatory properties as IL 1β. IL-1α can translocate to the nucleus and participates as a transcription factor for pro-inflammatory genes. With cell death, the IL-1α precursor is released and is biologically active. To date there are no reports of hyperglycemia influencing IL-1α localization and function in retinal cells. Thus, the focus of this study was to identify whether hyperglycemia influences IL-1α cellular localization, IL-1β mediated inflammatory signaling, and cell viability in Müller cells.

Methods: Müller cells were treated with normal (5mM) or high (25mM) glucose containing medium for 48 or 96 hours. Nuclear localization of IL-1α was determined using immunohistochemistry (IHC) or Western Blot analysis of nuclear fractions. Caspase-1 activity was measured in Müller treated with normal and high glucose medium in the presence or absence of a specific human monoclonal anti-human anti-IL-1α (10μg/ml) after 96 hours of treatment. Cell death was measured using Trypan Blue exclusion method.

Results: Hyperglycemia led to a significant decrease of 24±6% in active IL-1α in the cytosol of Müller. At 48 hours of high glucose treatment, IL-1α was predominantly cytosolic. At 96 hours of high glucose treatment, there was a significant, 3-fold increase in IL-1α levels in the nucleus. Nuclear IL-1α seemed clustered. Western Blot analysis of nuclear fractions confirmed increased nuclear localization of IL-1α at 96 hours. Anti-IL-1α treatment led to an 87±13.5% decrease in caspase activity and 76±14% decrease in cell death in Müller treated with high glucose.

Conclusions: Hyperglycemia alters cellular localization of IL-1α in Müller cells. For the first time, we have shown that under hyperglycemic conditions IL-1α influences activation of caspase-1 and thus the IL-1β pathway indicating that these members of the IL-1 family strongly regulate each other. Identifying the interaction between IL-1 family members is crucial for the understanding of the development of diabetic retinopathy.

Keywords: 557 inflammation • 490 cytokines/chemokines • 603 Muller cells  

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