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Role of ß-Adrenergic Receptors in Inflammatory Marker Expression in Müller Cells

¹From the Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois; and the ²Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee.

PURPOSE. To determine whether ß-adrenergic receptors are involved in the modulation of inflammatory cytokines in Müller cells in a hyperglycemic environment.

METHODS. Rat Müller cells were grown in high (25 mM)- or low (5 mM)-glucose medium. Müller cells lysates were processed for real-time polymerase chain reaction to measure steady state mRNA expression for the following inflammatory markers: iNOS, TNF-, IL-1B, and ICAM-1. Western blot analysis and ELISA assays were performed to determine the protein levels of these inflammatory markers and PGE2 content.

RESULTS. Isoproterenol treatment significantly decreased protein levels of iNOS, TNF-, and IL-1B, in rMC-1 cells cultured in high glucose as early as 1 hour, compared with cells receiving no treatment. PGE2 content was also reduced after isoproterenol treatment. There were no significant changes observed in protein levels of ICAM-1 production after isoproterenol treatment in high glucose. Steady state mRNA levels for iNOS were significantly decreased 1 hour after isoproterenol, whereas ICAM-1 gene expression was significantly increased after 1 hour. Isoproterenol significantly increased gene expression for IL-1B after 24 hours of treatment.

CONCLUSIONS. These results suggest that stimulation of ß-adrenergic receptors with isoproterenol leads to decreased levels of PGE₂, TNF-, and IL-1B protein content, and in both gene expression and protein levels of iNOS in Müller cells cultured in hyperglycemia. ß-Adrenergic receptor agonists had limited effects on ICAM-1 protein production. These results indicate that isoproterenol treatment reduces cytokine activation in cultured rat Müller cells.

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