Glucocorticoids attenuate interleukin ‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells

AbstractInterleukin ‐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 glucocorticoid s 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 signallin g 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. By 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‐...

Source: Journal of Neurochemistry - January 17, 2021 Category: Neuroscience Authors: Hannes Bongartz, Elena Anne Sei ß, Jörg Bock, Fred Schaper Tags: ORIGINAL ARTICLE Source Type: research