Somatostatin and gamma-aminobutyric acid inhibit interleukin-1 beta-stimulated release of interleukin-6 from rat C6 glioma cells.
OBJECTIVE
We investigated the ability of inhibitory neurotransmitters to alter the interleukin-1 beta (IL-1 beta)-stimulated release of interleukin-6 (IL-6) from cultured glial tumor cells.


METHODS
C6 rat glioblastoma cells were exposed to either IL-1 beta or its putative second messenger lysophosphatidylcholine (LPC) in the absence or presence of the inhibitory neurotransmitters somatostatin (SRIF) or gamma-aminobutyric acid (GABA). Alternatively, C6 cells were pretreated with selective inhibitors of JNK or p38 and then exposed to either IL-1 beta or LPC to determine the relative involvement of these terminal stress kinases in the stimulation of IL-6 release.


RESULTS
IL-1 beta promoted the release of IL-6 with a maximally effective concentration of 25 ng/ml. Both SRIF-14 and SRIF-28 comparably suppressed stimulated IL-6 release with an ED(50) of approximately 50 nM. GABA also prevented IL-1 beta-driven IL-6 release (ED(50) = 100 microM). IL-1 beta and LPC synergistically enhanced release of IL-6 in the presence of the beta-adrenergic receptor agonist isoproterenol (ISO); these effects were largely reversed by SRIF or GABA. The pyridinylimidazole inhibitor of p38, SB-203580, completely blocked stimulation of IL-6 release by IL-1 beta or LPC; conversely, the anthrapyrazolone JNK inhibitor, SP-600125, was ineffective in modifying stimulated IL-6 release.


CONCLUSIONS
The effects of IL-1 beta and LPC on IL-6 release from glioma cells are effectively antagonized by the inhibitory neurotransmitters SRIF and GABA. On the basis of correlative studies, we propose that the ability of inhibitory transmitters such as SRIF and GABA to counter the induction of IL-6 release may entail suppression of p38 activity.
Spangelo
Bryan L
BL
Department of Chemistry, University of Nevada at Las Vegas, Las Vegas, NV 89154-4003, USA. spangelo@ccmail.nevada.edu
Horrell
Scott
S
Goodwin
Amy L
AL
Shroff
Sachin
S
Jarvis
W David
WD
D000818:Animals; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma; D006825:Hybridomas; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects / Q000276:immunology; D013004:Somatostatin / Q000494:pharmacology*; D053561:Somatostatin-28; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D053561:Somatostatin-28; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases