Department of Anesthesiology
Timing-Dependent Glucocorticoid Regulation of Macrophage–Endothelial Crosstalk under Simulated Microgravity
Timing-Dependent Glucocorticoid Regulation of Macrophage–Endothelial Crosstalk under Simulated Microgravity
Altered gravity and neuroendocrine stress can perturb innate immune and vascular function during spaceflight. Especially microgravity has been proven to induce immune function which can be, however, counteracted by hypergravity. Moreover, different impact of either acute or chronic glucocorticoid treatment on monocyte and macrophage functions was demonstrated previously in an in vitro model.
The aim of the project is to investigate, if the timing of glucocorticoid exposure representing neuroendocrine stress differentially regulates macrophage inflammasome activation and pyroptosis under simulated microgravity, resulting in distinct patterns of macrophage-endothelial crosstalk and endothelial activation.
The findings of this study may support the selection of mechanistic immune-biomarkers and the design of countermeasure studies for prolonged space missions. The framework may also be relevant to terrestrial settings in which inflammatory, mechanical, and neuroendocrine stresses coexist.
| Work Package (WP) | Months | Activities and decision points |
|---|---|---|
| WP1: Platform establishment | 1-9 | Technical training; qualification of the altered-gravity platform; reproduction of the hydrocortisone–pyroptosis model; factorial pilot; selection of the primary endpoint and formal power calculation. |
| WP2: Macrophage interaction study | 7-22 | Confirmatory gravity-by-hydrocortisone experiments; orthogonal pyroptosis assays; assessment of reproducibility across independent experimental runs. |
| WP3: Endothelial transfer and mechanism | 18-34 | Conditioned-medium transfer; hydrocortisone-carryover controls; endothelial imaging and flow-adhesion experiments; focused pathway perturbation. |
| WP4: Validation and countermeasure | 30-41 | Independent replication; validation on an orthogonal platform or in primary cells if feasible; evaluation of hypergravity preconditioning. |
| WP5: Integration and thesis | 38-48 | Final statistical analysis; manuscript preparation; thesis writing; presentation of findings and preparation for the doctoral defense. |