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

摘要: Interleukin-6 (IL-6) is a cytokine primarily known for immune regulation. There also growing evidence that IL-6 triggers neurogenesis and impacts neural development, both life-long occurring processes can be impaired by early-life adult stress. Stress induces the release of glucocorticoids activation hypothalamic-pituitary-adrenal (HPA) axis. On cellular level, act via ubiquitously expressed glucocorticoid receptor. Thus, we aimed to elucidate whether affect IL-6-induced development. Here, show signalling neurite outgrowth in adrenal pheochromocytoma PC12 cells mitogen-activated protein kinase (MAPK) pathway-dependent manner, since was diminished upon Mek-inhibitor treatment. Using quantitative biochemical approaches, such as qRT-PCR analysis Hyper-IL-6 treated cells, induced accompanied early transient MAPK-dependent mRNA expression immediate genes coding proteins growth response 1 (Egr1) c-Fos. This correlates with reduced proliferation prolonged G0/G1 cell cycle arrest determined monitoring DNA content using flow cytometry. These results indicate signalling-induced differentiation. Interestingly, Dexamethasone impairs c-Fos Egr1 restrains outgrowth. Impaired development implicated aetiology neuropathologies. it appears likely stress-induced glucocorticoids, well therapeutically administered contribute neuropathologies reducing c-Fos, restraining IL-6-dependent