Glucocorticoids prime the inflammatory response of human hippocampal cells through up-regulation of inflammatory pathways
Articolo
Data di Pubblicazione:
2020
Citazione:
Glucocorticoids prime the inflammatory response of human hippocampal cells through up-regulation of inflammatory pathways / M.A. Horowitz, A. Cattaneo, M.N. Cattaneo, N. Lopizzo, L. Tojo, N. Bakunina, K. Musaelyan, A. Borsini, P.A. Zunszain, C.M. Pariante. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - (2020). [10.1016/j.bbi.2020.03.012]
Abstract:
Increased pro-inflammatory cytokines and an overactive hypothalamic-pituitary-adrenal (HPA) axis have both been implicated in the pathogenesis of depression. However, these explanations appear contradictory because glucocorticoids are well recognised for their anti-inflammatory effects. Two hypotheses exist to resolve this paradox: the mediating presence of glucocorticoid receptor resistance, or the possibility that glucocorticoids can potentiate inflammatory processes in some circumstances. We sought to investigate these hypotheses in a cell model with significant relevance to depression: human hippocampal progenitor cells. We demonstrated that dexamethasone in vitro given for 24 hours and followed by a 24 hours rest interval before an immune challenge potentiates inflammatory effects in these neural cells, that is, increases the IL-6 protein secretion induced by stimulation with IL-1β (10 ng/mL for 24 hours) by + 49% (P < 0.05) at a concentration of 100 nM and by + 70% (P < 0.01) for 1 μM. These effects are time- and dose-dependent and require activation of the glucocorticoid receptor. Gene expression microarray assays using Human Gene 2.1st Array Strips demonstrated that glucocorticoid treatment up-regulated several innate immune genes, including chemokines and Nod-like receptor, NLRP6; using transcription factor binding motifs we found limited evidence that glucocorticoid resistance was induced in the cells. Our data suggests a mechanism by which stress may prime the immune system for increased inflammation and suggests that stress and inflammation may be synergistic in the pathogenesis of depression.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Chemokines; Cytokines; Depression; Dexamethasone; Glucocorticoid resistance; Glucocorticoids; Hippocampal progenitor cells; Inflammation; NLRP6; NOD-like receptor; Pro-inflammatory
Elenco autori:
M.A. Horowitz, A. Cattaneo, M.N. Cattaneo, N. Lopizzo, L. Tojo, N. Bakunina, K. Musaelyan, A. Borsini, P.A. Zunszain, C.M. Pariante
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