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Short‐term TNF‐Alpha treatment induced A 2B adenosine receptor desensitization in human astroglial cells
Author(s) -
Trincavelli Maria Letizia,
Tonazzini Ilaria,
Montali Marina,
Abbracchio Maria Pia,
Martini Claudia
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21611
Subject(s) - astrogliosis , cytokine , adenosine , receptor , proinflammatory cytokine , adenosine receptor , tumor necrosis factor alpha , adenosine a1 receptor , microbiology and biotechnology , biology , chemistry , medicine , endocrinology , pharmacology , agonist , inflammation , central nervous system
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. J. Cell. Biochem. 104: 150–161, 2008. © 2007 Wiley‐Liss, Inc.