Inflammatory Activation of Human Brain Endothelial Cells by Hypoxic Astrocytes <i>In Vitro</i> is Mediated by IL-1β
Bibliographic record
Abstract
Leukocyte infiltration into the brain contributes to the development of ischemic brain damage and is mediated by endothelial/leukocyte adhesion molecules, cytokines, and chemokines released by ischemic brain cells. In this study, we provide evidence that human astrocytes (FHAs) subjected to in vitro hypoxia produce proinflammatory mediator(s) capable of up-regulating inflammatory genes, including intercellular adhesion molecule-1, interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-8, and monocyte chemotactic protein-1 (MCP-1) in human cerebromicrovascular endothelial cells (HCECs). FHAS were exposed to hypoxia in an anaerobic chamber for 4 hours, followed by reoxygenation for 24 hours. Astrocyte-conditioned media (ACM) collected from normoxic FHAS or FHAS subjected to hypoxia/reoxygenation were applied to HCEC cultures for 4 to 24 hours. Semiquantitative reverse transcription-polymerase chain reaction, immunocytochemistry, and enzyme-linked immunosorbent assay demonstrated up-regulation of intercellular adhesion molecule-1 in HCECs exposed to hypoxic ACM. A pronounced elevation in cytokine IL-1beta and tumor necrosis factor-alpha, and chemokine IL-8 and MCP-1 mRNA, accompanied by increased release of immunoreactive cytokines and chemokines into cell media was observed in HCECs exposed to hypoxic ACM. Hypoxia/reoxygenation induced a transient (4 to 18 hours of reoxygenation) up-regulation of IL-1beta mRNA in FHAS and a two- to threefold increase in IL-1beta levels secreted into ACM. Pretreatment of FHAS with 10 micromol/L dexamethasone inhibited both hypoxia-induced expression/secretion of IL-1beta and the ability of hypoxic ACM to induce inflammatory phenotype in HCECs. The ability of hypoxic ACM to up-regulate inflammatory genes in HCECs was inhibited in the presence of IL-1 receptor antagonist (IL-1Ra) and by pretreating ACM with the blocking anti-IL-1beta antibody. These findings strongly implicate IL-1beta secreted by hypoxic astrocytes in triggering inflammatory activation of HCECs and thereby influencing inflammatory responses at the site of the blood-brain barrier.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".