Relationship between cAMP induced inhibition of human meningioma cell proliferation and autocrine secretion of interleukin-6.
Previous studies have suggested that activation of the adenylyl cyclase - cAMP system in meningiomas results in decreased mitosis. We have used meningioma cell culture to further investigate this phenomenon and to examine the potential role played by interleukin-6 (IL6). Incubation of cultured meningioma cells for 4-6 days with cholera toxin and theophylline, both of which increase intracellular cAMP levels, markedly stimulated IL6 secretion and inhibited cell growth rate. Similar effects were observed with 8-bromo-cAMP. In contrast, a neutralising polyclonal antibody against IL6 significantly stimulated meningioma proliferation and reduced the inhibitory effects of 8-bromo-cAMP. These results support the concept that IL6 acts as an autocrine / paracrine inhibitory factor for meningioma proliferation, and that the inhibition exerted by elevated intracellular cAMP levels may be at least partially mediated via increased secretion of the cytokine.
Hüttner
A
A
Department of Neurosurgery, Kopfklinikum, University of Erlangen-Nürnberg, Germany.
Lei
T
T
Fahlbusch
R
R
Schrell
W
W
Adams
E F
EF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009500:Neutralization Tests; D013806:Theophylline / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000906:Antibodies; D015850:Interleukin-6; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013806:Theophylline; D000242:Cyclic AMP