Barnea A, Roberts J, Keller P, Word R A
Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center at Dallas, 5373 Harry Hines Boulevard, Dallas, TX 75390-9032, USA.
Brain Res. 2001 Mar 30;896(1-2):137-45. doi: 10.1016/s0006-8993(01)02141-2.
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-1beta, we addressed the question: Does IL-1beta regulate NPY expression by the astrocytes? Primary astrocytes derived from the human fetal or rat neonatal cortex were cultured in serum-free medium. IL-1beta, but not IL-6 or TNF-alpha, led to an increase in NPY production dose-dependently. IL-1beta 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-1beta did not diminish upon sub-culture of the astrocytes (five passages). In addition, IL-1beta 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-1beta did not alter the abundance of cJun-mRNA. In summary, we demonstrate that IL-1beta 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.
先前的研究表明，星形胶质细胞培养物以一种受调控的方式表达神经肽Y（NPY），即佛波酯会导致前NPY-mRNA和NPY产量增加。在这方面，源自人类胎儿或大鼠新生大脑的星形胶质细胞的行为是相似的（《调节肽》75卷（1998年）第293页）。由于星形胶质细胞可能会暴露于高水平的白细胞介素-1β（IL-1β），我们提出了一个问题：IL-1β是否调节星形胶质细胞的NPY表达？源自人类胎儿或大鼠新生皮层的原代星形胶质细胞在无血清培养基中培养。IL-1β，而非IL-6或肿瘤坏死因子-α（TNF-α），剂量依赖性地导致NPY产量增加。IL-1β的作用在人类星形胶质细胞中表现出来，而在大鼠星形胶质细胞中未表现出来，并且它被IL-1受体拮抗剂完全消除。星形胶质细胞传代培养（五代）后对IL-1β的反应性并未降低。此外，IL-1β导致前NPY-mRNA丰度增加，这之前cFos-mRNA有快速短暂的增加，JunB-mRNA有快速持续的增加。与cFos/JunB不同，IL-1β并未改变cJun-mRNA的丰度。总之，我们证明IL-1β对星形胶质细胞中NPY表达的诱导具有物种和细胞因子特异性，并且涉及IL-1受体。此外，NPY表达的诱导之前是两种转录因子（cFos、JunB）表达的快速增加，这两种转录因子先前（《癌基因》9卷（1994年）第2369页；《神经化学杂志》70卷（1998年）第1887页）已涉及人类NPY基因的转录调控。
