The role of cytokine in neuronal injury was examined in rat pheochromocytom
a (PC12) cells under chemical hypoxia (i.e. KCN) and glucose deprivation. T
he mRNA levels of interleukin-1 alpha (IL-1 alpha), IL-6, and tumor necrosi
s factor-alpha (TNF-alpha) were measured by reverse transcription-polymeras
e chain reaction (RT-PCR) in PC12 cells exposed to 0.5 mn KCN for various t
ime intervals. Cytokine mRNA levels expressed to peak levels 30 minutes aft
er KCN treatment and declined gradually until 240 min. The IL-1 alpha activ
ity reached the highest levels 2 hr after the same KCN treatment. Under par
allel conditions, KCN increased cytosolic free calcium concentration ([Ca2](i)) in the absence of glucose. However, IL-1 alpha rnRNA induction by KCN
was not altered under calcium-free conditions in PC12 cells, indicating it
s induction was Ca2+-independent. However, the phosphatidylcholine (PC)spec
ific phospholipase C (PLC) inhibitor D609 decreased the KCN-induced IL-1 al
pha mRNA and protein in PC12 cells suggests that PC-PLC might play a role i
n cytokine induction during hypoxia. (C) 2000 Elsevier Science Inc. All rig
hts reserved.