Premium
Stimulation of Interleukin‐6 Secretion and Gene Transcription in Primary Astrocytes by Adenosine
Author(s) -
Schwaninger Markus,
Neher Mike,
Viegas Elizabeth,
Schneider Armin,
Spranger Matthias
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69031145.x
Subject(s) - adenosine , adenosine receptor , agonist , cgs 21680 , medicine , endocrinology , stimulation , biology , gene expression , secretion , chemistry , adenosine a1 receptor , microbiology and biotechnology , receptor , gene , biochemistry
Abstract: During cerebral ischemia, the expression of interleukin‐6 (IL‐6), which has neuroprotective properties, increases. To understand the underlying mechanism, the regulation of IL‐6 expression by neurotransmitters that accumulate during cerebral ischemia was investigated. Adenosine stimulated IL‐6 secretion in primary astrocytes four‐ to 10‐fold. The effect was concentration dependent, the EC 50 being ∼8 µ M . Although the nonselective analogue 2‐chloroadenosine (2CA) increased IL‐6 secretion to a similar extent, the A 1 ‐selective agonist N 6 ‐cyclopentyladenosine or the A 2a agonist CGS‐21680 had only a marginal effect on IL‐6 secretion. IL‐6 secretion stimulated by 2CA (10 µ M ) was inhibited by the nonselective adenosine antagonist 8‐( p ‐sulfophenyl)theophylline, whereas the A 1 ‐selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine or the A 2a ‐selective antagonist 8‐(3‐chlorostyryl)caffeine had no effect, to a concentration of 0.1 µ M . Transcription of the IL‐6 gene was investigated by transfecting primary astrocytes with a reporter fusion gene containing the human IL‐6 promoter (−179/+12). 2CA stimulated IL‐6 gene transcription 2.5‐fold. Mutations of the binding site for NF‐κB or NF‐IL6 abrogated the response to 2CA. Thus, an increase of extracellular adenosine during focal cerebral ischemia may stimulate IL‐6 expression via A 2b receptors. The induction of IL‐6 expression appears to involve a transcriptional effect that depends on NF‐κB and NF‐IL6.