INTERLEUKIN-1 EXPRESSION IS INDUCIBLE BY NERVE GROWTH-FACTOR IN PC12 PHEOCHROMOCYTOMA CELLS

Expression of the cytokine interleukin 1-alpha (IL-1-alpha) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-1-alpha, (ii) an ELISA, and (iii) a specific cell conversion bioassay based on the use of LBRM33-1A5 cells. IL-1-alpha mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-1-alpha in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-1-alpha-like immunoreactivity varied. The expression of IL-1-alpha, as studied at the mRNA level, was inducible by mouse nerve growth factor (7S NGF), and the gene product level was inducible in a dose- and time-dependent fashion by 7S NGF. The maximum induction corresponds to a 600% increase in IL-1-alpha-like immunoreactivity above the expression level found in noninduced cells and occurred after a 3-day incubation of the cells with NGF at 0.75-mu-g/ml of culture medium. The significance of the ability of NGF to induce IL-1 expression lies in the fact that IL-1 itself also acts as a growth factor that promotes glial proliferation and, even more importantly, IL-1 itself induces the expression of NGF at peripheral nerve injury [Lindholm, D., Heumann, R., Meyer, M. & Thoenen, H. (1987) Nature (London) 330, 658-659].