Effect of agonists of adenosine receptors on inflammatory markers in human Muller cells

We report the presence of adenosine receptors at molecular level and study their role in the inflammatory pathway under hyperglycemic condition. Human Muller cells were cultured in low (5 mM) and high (25 mM) glucose with 10% FBS and 1% P/S. Cells were starved in 0% FBS for 18 h and then treated with various agonists CCPA, CGS 21680, NECA and IB-MECA for 6, 12 and 24 h. The adenosine receptors were identified by immunocytochemistry. ELISA was used to measure the levels of TNF-α, IL-1β and ICAM 1. Four types of adenosine receptors (A1, A2A, A2B and A3) were identified in human Muller cells. TNF-α content increased after agonist A1 and A3 treatment, but decreased after agonist A2A and A2B treatment. There was no significant effect on ICAM-1 and IL-1β. Stimulation of human Muller cells with adenosine A2A agonist (CGS 21680) and adenosine A2B agonist (NECA) reduces the level of TNF-α when exposed to high glucose, whereas A1 adenosine agonist (CCPA) and A3 adenosine agonist (IB-MECA) both positively and negatively regulate the TNF-α in hyperglycemia. However, none of these agonists has any significant role in affecting ICAM-1 and IL-1β.