Overexpression of the autoantigen hnRNP-A2 (RA33), the tumour suppressor p53 and activated MAP-Kinase p38 in inflamed synovial tissue
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Notice bibliographique
Résumé
Overexpression of the nuclear autoantigen hnRNP-A2 (RA33) has recently been observed in synovial tissue of RA patients and TNF transgenic mice. To further investigate this issue expression of hnRNP-A2 was compared with that of two other hnRNP proteins, the closely related hnRNP-A1 (a rare autoantigen in RA) and the structurally different hnRNP-C (which is not an autoantigen). In addition, expression of the tumour suppressor p53 and the MAP-kinase p38 was studied. Synovial tissue of patiens with RA or osteoarthitis and specimen from patients with early arthritis of <1 year duration were analyzed by immunohistochemistry HnRNP-A2 was highly overexpressed in RA synovial tissue as compared to tissue of osteoarthritis patients, and most abundantly found in CD68-positive cells of the lining layer. The antigen was not only localized in the nucleus but also in the cytoplasm confirming previous observations. Nuclear overexpression was also observed for hnRNP-C, whereas expression of hnRNP-A1 appeared normal. Remarkably, in the majority of hnRNP-A2 expressing cells also the p53 tumor suppressor was overexpressed and aberrantly localized in the cytoplasm. Furthermore, the MAP-kinase p38 was acitvated in these cells as revealed by a monoclonal antibody specifically recognizing the phosphorylated (activated) form of this kinase. This indicated that cells over-expressing hnRNP-A2 and p53 had been activated by proinflammatory cytokines such as TNF or IL-1. A comparable result was obtained with tissue from patients with early arthritis, irrespectively of their diagnosis (RA or reactive arthritis). So far, the conditions that lead to aberrant expression of these proteins have not been clearly defined since even prolonged exposure of macrophages or synovial fibroblasts to TNF or IL-1 did not cause any changes in hnRNP-A2 expression or induce its cytoplasmic accumulation. This was only achieved by treatment with the RNA polymeraseII inhibitor actinomycin D which subsequently led to apoptosis and accumulation of hnRNP-A2 in apoptotic bodies. The state of chronic inflammation in the rheumatoid synovium seems to cause aberrant expression and/or modification of (some) proteins which may lead to loss of tolerance and induction of patholocigal autoimmune reactions in genetically susceptible individuals.
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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 | 0,001 | 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