Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells.

Abstract

Expression of the cytokine interleukin la (IL-la) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-la, (it) an ELISA, and (i) a specific cell conversion bioassay based on the use of LBRM33-1A5 cells. IL-la mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-la in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-la-like immunoreactivity varied. The expression of IL-la, 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 maxmum induction corresponds to a 600% increase in IL-la-like immunoreactivity above the expression level found in noninduced cells and occurred after Interleukin la and 13 (IL-la and IL-1p), the endogenous pyrogen/lymphocyte-activating factors were first identified as products of lipopolysaccharide-stimulated macrophages (1). Both IL-la and IL-1,B have numerous effects on the nervous system besides their role as immune mediators (2). The most important effects of IL-1 on the nervous system include stimulation of corticotropin releasing factor and corticotropin release (3), slow wave sleep (4), and fever (1).We have been focusing on the question of whether the neuronally active substances IL-la and IL-1,B could also be of neuronal origin. Recent reports indicate that IL-1-like immunoreactivity (IL-i-LI) can be found in the human hypothalamus (5) and the rat hippocampus and olfactory bulb (6). IL-1l3 mRNA has been detected in the rat hippocampus upon convulsant treatment (7) and was also found to be colocalized with nerve growth factor (NGF) mRNA in hippocampal pyramidal cells (8).We have earlier shown, by means of immunohistochemistry, that IL-la is localized in peripheral nerves (24) with a distribution closely resembling that of sympathetic noradrenergic innervation and in the noradrenergic chromaffin cells of the rat and mouse adrenal medulla (9). It was also shown that in vivo treatment of rats with cholinergic agonists, known to stimulate the release of the content of the chromaffin cells, caused a significant decline in the adrenal IL-la content. This suggests that IL-la can be released in a similar fashion to catecholamines, neuropeptide Y, and enkephalins (10).To further study the expression and release of IL-la in chromaffin cells, we have turned to the well-established pheochromocytoma PC12 cell line, which has been widely used as a model system in studies of sympathetic neuronal function and development. It also enabled us to examine the regulation of IL-la expression by NGF, which stimulates neurite outgrowth and regulates the expression of a wide variety of proteins in PC12 cells (11-13).The analysis of NGF effects on the expression of IL-1, in relation to the numerous neuronal effects of IL-1, is particularly interesting in view of the demonstration that IL-1 can induce...

Circulating Interleukin-1-Beta Levels after Acute and Prolonged Exposure to Low Temperatures: Human and Rat Studies

“…In a series of elegant papers, Bartfai and colleagues [10,11] showed that adrenal chromaffin cells and a chromaffin-related line, PC 12 pheochromocytoma cells, are endowed with IL-1 producing ability in vitro. These authors also demonstrated that IL-1-like immunoreactivity in the adrenal medulla was associated with the IL-1· isoform, and estimated the amount of cytokine to be 50 pg/mg of adrenal gland protein [15].…”

“…the chromaffin cells of the adrenal medulla, has also been reported [8][9][10]. In spite of extensive cellular and molecular characterization of IL-1 in different in vitro models of chromaffin cells [10,11], to our knowledge no study has thus far specifically investigated whether adrenal IL-1 plays a role in mediating HPA activation under stress conditions. Within this conceptual framework, the present study was established to investigate: (1) whether systemic IL-1 production undergoes significant changes in association with a physicoemotional type of stress, i.e.…”

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…NGF also directly stimulates degranulation of mast cells, increases the number of mast cells in peripheral tissues and promotes cell growth of myeloid cells (120,411,626), induces proliferation and differentiation of B cells, and enhances histamine release from basophils. NGF is also capable of stimulating IL-1 expression in PC12 cells and suppressing LTC 4 production in human eosinophils (13,846). Of note, NGF is upregulated in patients with atopic dermatitis, in which it may contribute to pruritus, mast cell stimulation, eosinophil activation, and keratinocyte dysfunction (reviewed in Refs.…”

Role of IL-1 b and TNF- a in the regulation of NGF in experimentally induced arthritis in mice

“…Since NGF promotes the synthesis of IL-1β [24] and TNF-α gene activation [25], we tested the effect of NGFAb on carrageenan-induced joint inflammation. The results, shown in Fig.…”