Corticosterone exerts immunostimulatory effects on macrophages via endoplasmic reticulum stress
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: : Glucocorticoids are the central effector hormones for the hypothalamic-pituitary-adrenal axis. However, the effects of endogenous glucocorticoids on the immune system are not understood completely. METHODS: : Macrophage function (adherence, chemotaxis and cytokine production) was assessed in the presence of increasing concentrations of corticosterone. The role of endoplasmic reticulum (ER) stress in corticosterone immunoregulation was determined with thapsigargin and plasmid pGCL-GFP-siXBP1. Mifepristone was used to determine the role of glucocorticoid receptor in the corticosterone-induced ER stress response. RESULTS: : Corticosterone exerted immunostimulatory effects on macrophage function at low concentrations. No effects were observed at high concentrations in the absence of immunological stimulation. Low-dose corticosterone induced ER stress, which was correlated to the corticosterone immunostimulatory activities. Expression of X box-binding protein (XBP) 1, but not activating transcription factor 6, was significantly increased at both mRNA and protein levels only in the presence of low-dose corticosterone. Inhibition of XBP1 expression with small interfering RNA significantly inhibited the corticosterone immunostimulatory effects. In addition, pretreatment of macrophages with mifepristone significantly inhibited the expression of glucose response protein 78 and XBP1 in macrophages by low-dose corticosterone. CONCLUSION: : At low concentrations, endogenous glucocorticoids exert immunostimulatory actions on macrophages. The underlying mechanisms may be correlated to ER stress via the glucocorticoid receptor, in which XBP1 plays an important role.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it