title: Short-term TNF-Alpha treatment induced A2B adenosine receptor desensitization in human astroglial cells.
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 (A(2B) 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 A(2B) 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 A(2B) AR phosphorylation inducing, in turn, impairment in A(2B) 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 A(2B) AR functional responses. The results may indicate the A(2B) AR functional impairment as a cell defense mechanism to counteract the A(2B) receptor-mediated effects during the acute phase of brain damage, underlying A(2B) AR as a target to modulate early inflammatory responses.
authors.affiliation: Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Trincavelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Tonazzini
authors.forename: Marina
authors.initials: M
authors.lastname: Montali
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Abbracchio
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D001253:Astrocytes / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D007700:Kinetics; D010766:Phosphorylation; D011493:Protein Kinase C; D043704:Receptor, Adenosine A2B / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D043704:Receptor, Adenosine A2B; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D011493:Protein Kinase C