Differential regulation of baculoviral repeat containing protein 2 (BIRC2) and 3 (BIRC3) by inflammatory stimuli and glucocorticoids
Notice bibliographique
Résumé
Introduction Glucocorticoids (GCs) act, via the glucocorticoid receptor (GR) to, repress expression of many inflammatory genes and are widely used to treat inflammatory diseases. However, GCs also induce expression of some inflammatory genes. Examples include, BIRC3, and the closely related homolog, BIRC2. While, it is unclear why GCs may up‐regulate such genes, BIRC2 and BIRC3 are suggested to be functionally redundant E3 ubiquitin ligases that may contribute to inflammatory signaling cascades. In the current study pulmonary A549 cells are used as a model of airway epithelial cells to characterize the expression of BIRC2 and BIRC3 in the context of inflammatory stimuli and GCs. Methods A549 cells were treated for various times with dexamethasone (Dex), budesonide (Bud), IL1B and TNF alone or in combination. Concentration‐response analyses established maximally‐effective concentrations for Dex (1µM), Bud (333nM), IL1B (1ng/ml) and TNF (10ng/ml). Roles for GR and the NF‐κB pathway were interrogated by gene silencing, the GR receptor antagonist, Org34517, adenoviral‐mediated overexpression of a dominant inhibitor of NF‐κB, IκBαDN, or ATP binding‐site IκB kinase (IKK) inhibitors. Cells were harvested for: i) total RNA, prior to cDNA synthesis and qPCR analysis of gene expression; or ii) total proteins and western blot analysis. ChIP‐PCR for both GR and NF‐κB (RELA) was performed 1 h following IL1B, Bud IL1B+Bud. Results Low baseline expression of BIRC3 mRNA was induced 60‐, 25‐ or 10‐fold by IL1B, TNF, or GCs, respectively. Peak BIRC3 mRNA expression occurred at 4h for IL1B and TNF, but at 6‐24h for GCs. In each case, maximal BIRC3 protein expression occurred 6‐24h post‐treatment and this was unaffected by combination treatment (IL1B/Dex or TNF/Dex). While, BIRC2 mRNA was modestly induced by all stimuli (<5‐fold), protein expression was constitutive. Gene silencing and receptor antagonism by Org34517 confirmed a role for GR in BIRC3 expression induced by GCs. Likewise, silencing of the NF‐κB subunit, RELA, and the IKK2‐selective inhibitors, PS‐1145 or ML120B, reduced BIRC3 expression induced by IL1B. Additionally, complete loss of IL1B‐induced BIRC3 and BIRC2 mRNA expression was observed following overexpression of IκBαDN. Furthermore, ChIP‐PCR analysis confirmed IL1B‐induced binding of RELA and GC‐induced binding of GR upstream of the BIRC3 gene. Conclusions While our data show constitutive expression of BIRC2 protein, which may indicate an acute role in inflammatory signaling, the later induction of BIRC3 expression via an NF‐κB‐dependent mechanism suggests a delayed and possibly nonredundant function relative to BIRC2. The modest induction of BIRC3 expression by GCs involves the GR but is currently of unclear significance. Given there is no loss of GR or NF‐κB recruitment to the BIRC3 locus with co‐treatment by IL1B+GC, we propose roles for both factors in maintaining BIRC3 expression in the presence of an inflammatory stimulus plus a GC.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
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 | 0,000 | 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».