Interleukin-1β induces expression of neuropeptide Y in primary astrocyte cultures in a cytokine-specific manner: induction in human but not rat astrocytes

Previous studies have demonstrated that astrocyte cultures express neuropeptide Y (NPY) in a regulated manner, namely, phorbol ester leads to an increase in proNPY–mRNA and NPY production. In this respect, the behavior of astrocytes derived from the human fetal or rat neonatal brain is similar (Regul. Pept. 75 (1998) 293). Since astrocytes can be exposed to high levels of IL-1β, we addressed the question: Does IL-1β regulate NPY expression by the astrocytes? Primary astrocytes derived from the human fetal or rat neonatal cortex were cultured in serum-free medium. IL-1β, but not IL-6 or TNF-α, led to an increase in NPY production dose-dependently. IL-1β action manifested in the human but not in the rat astrocytes and it was completely abolished by IL-1 receptor antagonist. The responsiveness to IL-1β did not diminish upon sub-culture of the astrocytes (five passages). In addition, IL-1β led to an increase in the abundance of proNPY–mRNA, which was preceded by a rapid and transient increase in cFos–mRNA and a rapid and sustained increase in JunB–mRNA. In contrast to cFos/JunB, IL-1β did not alter the abundance of cJun–mRNA. In summary, we demonstrate that IL-1β induction of NPY expression in astrocytes is species- and cytokine-specific and that IL-1 receptor is involved. Moreover, induction of NPY expression is preceded by a rapid increase in the expression of two transcription factors (cFos, JunB) that have been previously (Oncogene 9 (1994) 2369; J. Neurochem. 70 (1998) 1887) implicated in transcriptional regulation of the human NPY gene.