In search of signals that trigger GPR17 expression in microglia cells

After insults microglia cells act by migrating to the site of injury, phagocyting cell debris and secreting inflammatory mediators, among which are cytokines, chemokines, cysteinyl leukotrienes (cysLTs) and purinergic molecules. The recently discovered GPR17 is structurally related to P2Y purinergic and cysLT receptors. Little is known about its regulation in microglia except that, in animal models, GPR17 was found in these cells exclusively after ischemic injury. The aim of this study was to identify in vitro signals that can trigger GPR17 expression in reactive microglia in vivo. Realtime PCR showed that in primary rat microglia cells, a low level of GPR17 can be increased by conditioned medium from oxygen and glucose deprived neurons or by prolonged deprivation of growth factors, but not by typical “danger signals” like ATP or cysLT. Among other known activators of microglia cells, lipopolysaccharide caused a decrease of GPR17 expression, but GPR17 receptor agonists and zymosan (a stimulator of phagocytosis) led to its increase in a time-dependent manner. It is still not known how long, after induction, GPR17 receptors remain in the membrane and what function they may play. However preliminary results showed that GPR17 expression may participate in the acquisition of a detrimental or a beneficial phenotype of microglia.