Long-term glial cell treatment with the proinflammatory cytokine TNF-alpha has been demonstrated to increase the functional responsiveness of A 2B adenosine receptors (A2B ARs), which in turn synergize with the cytokine inducing chronic astrogliosis. In the present study, we investigated the short-term effects of TNF-alpha on A2B AR functional responses in human astroglial cells (ADF), thus simulating the acute phase of cerebral damage which is characterized by both cytokine and adenosine high level release. Short-term TNF-alpha cell treatment caused A2B AR phosphorylation inducing, in turn, impairment in A2B AR-G protein coupling and cAMP production. These effects occurred in a time-dependent manner with a maximum following 3-h cell exposure. Moreover, we showed PKC intracellular kinase is mainly involved in the TNF-alpha-mediated regulation of A2B AR functional responses. The results may indicate the A 2B AR functional impairment as a cell defense mechanism to counteract the A2B receptor-mediated effects during the acute phase of brain damage, underlying A2B AR as a target to modulate early inflammatory responses. © 2007 Wiley-Liss, Inc.
Short-term TNF-alpha treatment induced A2B adenosine receptor desensitization in human astroglial cells
TONAZZINI, ILARIA;
2008
Abstract
Long-term glial cell treatment with the proinflammatory cytokine TNF-alpha has been demonstrated to increase the functional responsiveness of A 2B adenosine receptors (A2B ARs), which in turn synergize with the cytokine inducing chronic astrogliosis. In the present study, we investigated the short-term effects of TNF-alpha on A2B AR functional responses in human astroglial cells (ADF), thus simulating the acute phase of cerebral damage which is characterized by both cytokine and adenosine high level release. Short-term TNF-alpha cell treatment caused A2B AR phosphorylation inducing, in turn, impairment in A2B AR-G protein coupling and cAMP production. These effects occurred in a time-dependent manner with a maximum following 3-h cell exposure. Moreover, we showed PKC intracellular kinase is mainly involved in the TNF-alpha-mediated regulation of A2B AR functional responses. The results may indicate the A 2B AR functional impairment as a cell defense mechanism to counteract the A2B receptor-mediated effects during the acute phase of brain damage, underlying A2B AR as a target to modulate early inflammatory responses. © 2007 Wiley-Liss, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
