Interleukin‐3 and Interleukin‐3 Receptors in the Brain^a

Abstract

We have previously demonstrated that interleukin 3 (IL-3) has a neurotrophic effect on central cholinergic neurons and have demonstrated the presence of IL-3 receptor (IL-3R)beta subunits in septal cholinergic neurons by reverse-transcribed polymerase chain reaction (RT-PCR) and immunohistochemistry. In order to confirm that the expressed IL-3R is functional, we conducted experiments to show an alpha subunit of IL-3R. The alpha subunit was clearly demonstrated by RT-PCR in the central cholinergic neuronal hybrid cell line SN6, but not in its mother cell line N18TG2, and the expression was slightly upregulated after IL-3 treatment. Choline acetyltransferase and vesicular acetylcholine transporter mRNAs were significantly increased in SN6 after treatment with IL-3. Immunohistochemically, IL-3R alpha-positive cells were mainly present in the medial septal and basal forebrain region, and the stained cells were similar to choline acetyltransferase-positive cells in shape and distribution. The IL-3R alpha-positive cells slightly increased two days after fimbria-fornix transection and decreased seven days after. These findings suggest that functional IL-3 receptors are expressed in the central cholinergic neurons and contribute to some physiological roles such as the differentiation and maintenance of these neurons.

Erythropoietin mediates tissue protection through an erythropoietin and common β-subunit heteroreceptor

“…In the mouse, therefore, the ␤cR knockout will affect only GM-CSF and IL-5 signaling (26), not IL-3, which has itself been reported to possess tissue-protective properties. Notably, IL-3 and its receptors (both ␣ and ␤) are locally made (27,28) and act in a neurotrophic and neuroprotective manner (29,30), including protection from spinal motor neuron transection (31). To answer this question, additional experiments using genesilencing technology will need to be performed in another species, e.g., in the rat, for which abundant data relevant to tissue protection have been collected.…”

Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias

“…[40][41][42] In vivo toxicology studies in animals with cross-reactive receptors will be necessary to address potential non-hematopoietic toxicities.…”

Neurotrophic Effect of Interleukin‐3 (IL‐3) and Its Mechanisms of Action in the Nervous System1

“…IL-3 also increases ChAT activity in cholinergic cell line SN6 (20,29,72). IL-3R α and β subunits are found in cholinergic neurons in cultures and also in sections from the basal forebrain of mice and rats (35,71,72). These findings strongly suggest that such in vitro IL-3 effects are directly mediated via IL-3R expression in cholinergic neurons.…”

“…IL-3 is shown to increase expression of IL-3R mRNA, especially the β subunit mRNA in cholinergic cell line SN6 (35,71). SN6 expresses IL-3R mRNA for both α and β subunits, but another cholinergic cell line, SN49, expresses only α subunit mRNA (35).…”