Abstract

We have previously shown that activation of the phosphatidyl-inositol/phospholipase C pathway could induce interleukin 6 (IL-6) release from U373MG human astrocytoma cells. We also found that, although interleukin 1β (IL-1β) did not activate phosphatidylinositol turnover, it induced a robust release of IL-6. In the present study, we examined the role of adenylate cyclase/cyclic 3′,5′-adenosine monophosphate (cAMP) pathway in IL-6 release. Agents which mimicked (dibutyryl cAMP) or stimulated (isoproterenol and forskolin) cAMP formation were found to induce IL-6 release and their effects could be potentiated by 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. On the other hand, in spite of its robust action on IL-6 release, IL-1β did not stimulate cAMP formation. Other possible signal transduction mechanisms involved in IL-1β-induced IL-6 release are discussed.

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