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Vasoactive Intestinal Peptide and Forskolin Stimulate Interleukin 6 Production by Rat Cortical Astrocytes in Culture via a Cyclic AMP‐Dependent, Prostaglandin‐Independent Mechanism
Author(s) -
Grimaldi Maurizio,
Pozzoli Giacomo,
Navarra Pierluigi,
Preziosi Paolo,
Schettini Gennaro
Publication year - 1994
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.1471-4159.1994.63010344.x
Subject(s) - forskolin , vasoactive intestinal peptide , medicine , endocrinology , prostaglandin e2 , protein kinase a , prostaglandin e , stimulation , prostaglandin , protein kinase c , cytokine , biology , chemistry , signal transduction , kinase , microbiology and biotechnology , receptor , neuropeptide
Abstract: In this study we analyzed the involvement of the cyclic AMP (cAMP)‐protein kinase A system in the regulation of interleukin 6 production by cultured cortical astrocytes. Vasoactive intestinal peptide strongly increased, in a dose‐dependent manner, interleukin 6 production. This effect was reduced when protein kinase A was blocked by KT‐5720; it was not affected by calphostin C, a protein kinase C inhibitor. Forskolin caused a concentration‐dependent increase in interleukin 6 release that was also inhibited by KT‐5720. Because prostaglandins are believed to play a role in interleukin 6 production, we tried to determine whether the stimulatory effects of vasoactive intestinal peptide and forskolin on cytokine release might be mediated by stimulation of prostaglandin production in cortical astrocytes. Vasoactive intestinal peptide did not increase the production of either prostaglandin E 2 or F 2α . Conversely, forskolin concentration‐dependently stimulated the production of both prostaglandins, an effect that was blocked by indomethacin. Indomethacin did not affect either vasoactive intestinal peptide‐ or forskolin‐stimulated interleukin 6 production. To exclude the possibility that prostaglandins participate in interleukin 6 production induced by forskolin, we tested prostaglandins E 2 and F 2α . The former was completely ineffective in eliciting the cytokine production, whereas prostaglandin F 2α slightly increased interleukin 6 production only at the highest concentrations. 8‐Bromo‐cAMP and dibutyryl‐cAMP stimulated interleukin 6 production to a lesser extent than vasoactive intestinal peptide and forskolin. In conclusion, we provide evidence that vasoactive intestinal peptide increases interleukin 6 production by astrocytes through the stimulation of the cAMP‐protein kinase A pathway, an effect that is reproduced by cAMP analogues. In addition, we point out that prostaglandins are not involved in vasoactive intestinal peptide‐ and forskolin‐mediated induction of interleukin 6 production in cultured astrocytes.