Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/96522
Title: Glucocorticoids attenuate interleukin‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells
Author(s): Bongartz, Hannes
Seiß, Elena Anne
Bock, Jörg
Schaper, Fred
Issue Date: 2021
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-984791
Subjects: Glucocorticoids
Neuritogenesis
Interleukin-6 (IL-6)
Stress
Abstract: Interleukin-6 (IL-6) is a cytokine primarily known for immune regulation. There is also growing evidence that IL-6 triggers neurogenesis and impacts neural development, both life-long occurring processes that can be impaired by early-life and adult stress. Stress induces the release of glucocorticoids by activation of the hypothalamic–pituitary– adrenal (HPA) axis. On the cellular level, glucocorticoids act via the ubiquitously expressed glucocorticoid receptor. Thus, we aimed to elucidate whether glucocorticoids affect IL-6- induced neural development. Here, we show that IL-6 signalling induces neurite outgrowth in adrenal pheochromocytoma PC12 cells in a mitogen-activated protein kinase (MAPK) pathway-dependent manner, since neurite outgrowth was diminished upon Mek-inhibitor treatment. Using quantitative biochemical approaches, such as qRT-PCR analysis of Hyper-IL- 6 treated PC12 cells, we show that neurite outgrowth induced by IL-6 signalling is accompanied by early and transient MAPK-dependent mRNA expression of immediate early genes coding for proteins such as early growth response protein 1 (Egr1) and c-Fos. This correlates with reduced proliferation and prolonged G0/G1 cell cycle arrest as determined by monitoring the cellular DNA content using flow cytometry. These results indicate for IL-6 signalling-induced neural differentiation. Interestingly, the glucocorticoid Dexamethasone impairs early IL-6 signalling-induced mRNA expression of c-Fos and Egr1 and restrains neurite outgrowth. Impaired Egr1 and c-Fos expression in neural development is implicated in the aetiology of neuropathologies. Thus, it appears likely that stress-induced release of glucocorticoids, as well as therapeutically administered glucocorticoids, contribute to the development of neuropathologies by reducing the expression of Egr1 and c-Fos, and by restraining IL-6- dependent neural differentiation.
URI: https://opendata.uni-halle.de//handle/1981185920/98479
http://dx.doi.org/10.25673/96522
Open Access: Open access publication
License: (CC BY-NC-ND 4.0) Creative Commons Attribution NonCommercial NoDerivatives 4.0(CC BY-NC-ND 4.0) Creative Commons Attribution NonCommercial NoDerivatives 4.0
Sponsor/Funder: Projekt DEAL 2021
Journal Title: Journal of neurochemistry
Publisher: Wiley-Blackwell
Publisher Place: Oxford
Volume: 157
Issue: 3
Original Publication: 10.1111/jnc.15305
Page Start: 532
Page End: 549
Appears in Collections:Fakultät für Naturwissenschaften (OA)

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