Interleukin-5 receptor alpha chain expression and splicing during brain development in mice.
We have studied the IL-5 production and responsiveness in the mouse brain. Both IL-5 and IL-5 receptor alpha chain (IL-5 Ralpha) were expressed in vitro in astrocytes, but not in neurons. IL-5 was expressed at constant levels during brain development, after birth, and in the adult brain of both normal mice and mice bearing infection or allergic reaction associated with high Th2 lymphocyte reactivity. Conversely, expression of IL-5 Ralpha was highly regulated both in quantitative terms and in the number of alternatively spliced isoforms. In embryos, we observed the classical transmembrane isoform and two new larger ones, in addition to three smaller soluble isoforms. At birth, a single soluble isoform was generated, and in the post-natal period, the major transmembrane and two or three soluble isoforms were detected. In adulthood, no expression of IL-5 Ralpha was detected in normal mice, but all the isoforms were produced in mice with inflammatory reactions. We propose that IL-5 has a specific autocrine and/or paracrine function in astrocytes, maintaining the homogeneity of the activation state in a given astrocyte population. The alternative splicing of IL-5 Ra modulates the brain tissue from the fully unresponsive to the highly sensitive state in regard to IL-5 stimulation. According to our results, IL-5 Ralpha splicing is controlled by an intrinsic program in the brain during the embryonic and postnatal periods, and an extrinsic systemic program reflecting the inflammatory reactions associated with high systemic IL-5 levels.
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Departmento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Borojevic
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D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D007249:Inflammation; D051379:Mice; D008809:Mice, Inbred C3H; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000737:chemistry*; D053649:Receptors, Interleukin-5; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D020033:Protein Isoforms; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5