Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP‐1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokines
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Notice bibliographique
Résumé
Accumulating evidence supports the existence of an innate immune response in the brain during systemic inflammation that is associated with a robust induction of proinflammatory cytokines and chemokines by specific cells of the central nervous system. The present study investigated the genetic regulation and fine cellular distribution of the monocyte chemoattractant protein-1 (MCP-1) in the brain of mice and rats in response to systemic immune insults. MCP-1 belongs to a superfamily of chemokines that have a leading role in the early chemotaxic events during inflammation. In situ hybridization histochemistry failed to detect constitutive expression of the chemokine transcript in the cerebral tissue except for the area postrema (AP) that exhibited a low signal under basal conditions. This contrasts with the strong and transient induction of the mRNA encoding MCP-1 following a single systemic bolus of lipopolysaccharide (LPS), recombinant interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). These stimuli rapidly triggered (30 to 90 minutes) MCP-1 transcription in all the circumventricular organs (CVOs), the choroid plexus (chp), the leptomeninges, and along the cerebral blood vessels. The time-related induction and intensity of the signal differed among the challenges, route of administration and species, but MCP-1-expressing cells were always found in vascular-associated structures and those devoid of blood-brain barrier. At later times, few isolated microglia across the brain parenchyma depicted positive signal for MCP-1 mRNA. A dual-labeling procedure also provided convincing anatomical evidence that endothelial cells of the microvasculature and a few myeloid cells of the CVOs and chp were positive for the transcript during endotoxemia. This gene is under a sophisticated transcriptional regulation, as the hybridization signal returned to undetectable levels 12 to 24 hours after all the treatments in both species. Of interest are the data that only ligands that triggered nuclear factor kappa B (NF-kappa B) signaling had the ability to increase MCP-1 gene expression, because high doses of IL-6 remained without effects. These data provide the anatomical evidence that MCP-1 is expressed within specific populations of cells in response to systemic inflammatory molecules that use NF-kappa B as intracellular signaling system. This chemokine may therefore play a critical role in the cerebral innate immune response and contribute to the early chemotaxic events during chronic cerebral inflammation.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle