Functional characterization of substance P receptors on cultured human spinal cord astrocytes: Synergism of substance P with cytokines in inducing interleukin-6 and prostaglandin E2 production
✍ Scribed by Carla Palma; Luisa Minghetti; Mara Astolfi; Elena Ambrosini; Francesca Ceccherini Silberstein; Stefano Manzini; Giulio Levi; Francesca Aloisi
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 160 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Following brain injury, astrocytes express receptors for cytokines and neuropeptides and secrete several regulatory mediators that have a well established role in inflammation, immunity, and tissue development or repair. To elucidate the role of substance P (SP), a neurotransmitter peptide of the tachykinin family, in inducing astrocyte secretory activities, we have examined the expression of SP receptors and the functional consequences of their activation in cultured astrocytes from the human embryonic brain or spinal cord. Radioligand binding studies revealed that only one type of SP receptors, the high affinity NK-1 receptor, was present on human astrocytes and that spinal cord astrocytes expressed about 6 times as many SP binding sites as brain astrocytes. Following SP treatment, a substantial inositol phosphate formation was observed in spinal cord astrocytes only. Stimulation of spinal cord astrocytes with SP alone did not induce secretion of cytokines [interleukin-6 (IL-6), granulocyte-macrophage-CSF, macrophage chemoattractant protein-1 or leukemia inhibitory factor] or prostaglandin E 2 (PGE 2 ). Interestingly, however, SP selectively potentiated the inducing effect of IL-1 on IL-6 and PGE 2 secretion by spinal cord astrocytes without affecting the IL-1--evoked secretion of other cytokines. SP also enhanced the small inducing effect of tumor necrosis factor-␣ (TNF-␣) on IL-6 and PGE 2 secretion and that of transforming growth factor- on PGE 2 secretion. These results suggest that SP can enhance immunoregulatory and neurotrophic astroglial functions mediated by IL-6 and PGE 2 by acting in concert with a set of cytokines whose cerebral expression has been reported during development and in a variety of diseases.