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Published on: January 22, 2019
Genomic and non-genomic effects of different glucocorticoids on mouse thymocyte apoptosis
Stefano Bruscoli1, Rosa Di Virgilio, Valerio Donato
1Department of Clinical and Experimental Medicine, Section of Pharmacology, Perugia University Medical School, Via del Giochetto, 06122 Perugia, Italy.
Abstract:
Glucocorticoids, widely used therapeutic agents for several pathologies, act upon diverse cells and tissues, including the lympho-haemopoietic system. Glucocorticoid-mediated apoptosis has been described as one of the mechanisms underlying their pharmacological and physiological effects. Glucocorticoids induce apoptosis in thymocytes through genomic and non-genomic signals. We tested thymocyte apoptosis rates as induced by a panel of glucocorticoids. Using four glucocorticoids that are widely adopted in clinical practice we compared their induction of thymocyte apoptosis and activation of non-genomic and genomic signals, including phosphatidylinositol-specific phospholipase C (PI-PLC), caspase-8, -9 and -3, and Glucocorticoid-Induced Leucine Zipper (GILZ). GILZ is a protein that is rapidly induced by glucocorticoids treatment and involved in apoptosis modulation. Results indicate different glucocorticoids have different apoptotic activity which is related to their ability to induce both genomic, evaluated as caspases activation and GILZ expression, and non-genomic effects, evaluated as PI-PLC phosphorylation.
Insights
Different glucocorticoids exhibit varying apoptotic effects on thymocytes. This variation correlates with their ability to trigger both genomic signals, like caspase activation and GILZ expression, and non-genomic signals, such as PI-PLC phosphorylation.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Glucocorticoids are widely used therapeutics impacting the lympho-haemopoietic system.
- Glucocorticoid-induced apoptosis is a key mechanism for their therapeutic and physiological effects.
- Apoptosis in thymocytes is mediated by both genomic and non-genomic signaling pathways.
Purpose of the Study:
- To compare the thymocyte apoptosis-inducing capacity of four clinically relevant glucocorticoids.
- To investigate the correlation between glucocorticoid apoptotic activity and the activation of specific genomic and non-genomic signals.
Main Methods:
- Assessed thymocyte apoptosis rates induced by various glucocorticoids.
- Measured activation of non-genomic signals, specifically phosphatidylinositol-specific phospholipase C (PI-PLC) phosphorylation.
- Evaluated genomic signals including caspase-8, -9, and -3 activation, and Glucocorticoid-Induced Leucine Zipper (GILZ) protein expression.
Main Results:
- Significant differences in thymocyte apoptosis induction were observed among the tested glucocorticoids.
- Apoptotic activity correlated with the capacity of glucocorticoids to activate PI-PLC.
- Glucocorticoid apoptotic potency also correlated with their ability to induce caspases activation and GILZ expression.
Conclusions:
- The apoptotic potency of glucocorticoids varies and is linked to their distinct genomic and non-genomic signaling profiles.
- Understanding these differential effects is crucial for optimizing glucocorticoid-based therapies.
- This study highlights the complex interplay of signaling pathways in glucocorticoid-induced thymocyte apoptosis.
