The Interactions Between Interferon-γ and Leukotriene D4 Signaling and Its Impact on Proliferative and Contractile Responses of Airway Smooth Muscle Cells
Notice bibliographique
Résumé
Rationale: Airway smooth muscle (ASM) tone contributes to airway hyperresponsiveness (AHR) and airflow limitation in asthma. Alterations in the airway smooth muscle cell (ASMC) characteristics associated with asthma, including hyperplasia and increased velocity of contraction, have been described. Interferon- (IFN-) is a signature T helper 1 effector cytokine that is upregulated in the airway in severe asthma. It is suggested to promote AHR and steroid-resistance. However, its potential impact on ASM function is largely unknown. Cysteinyl leukotrienes (CysLTs) are important inflammatory mediators in asthma. They are potent contractile agonists and have been shown to also induce ASMC proliferation. IFN- is reported to upregulate the expression of cysteinyl leukotriene receptor 1 (CysLTR1) in ASMCs. We hypothesized that priming ASMCs with IFN- would augment CysLT-mediated contractile and proliferative responses via the upregulation of CysLTR1. In current study, we explored the potential of the described interactions between IFN- and CysLT signaling in ASMCs. Methods: Human ASMC cultures were derived from transplant-grade lungs without any history of asthma. The contractility of the ASMCs was assessed with a collagen contraction assay, in which cells incorporated in collagen gels were treated with 1000 U/mL IFN- for 24 hours followed by challenges with 1 M leukotriene D 4 (LTD4), one of the CysLTs, or 100 M histamine. The gel area reduction 30 minutes following the challenge was recorded. ASMC proliferation, represented by DNA synthesis, was assessed by bromodeoxyuridine (BrdU) assay. Serum-starved control and IFN--primed ASMCs were treated with LTD4, 24-hour BrdU incorporation was assessed by flow cytometry. The effect of IFN- on CysLTR1 expression was assessed by Western blot and quantitative real-time PCR. Results: IFN- priming resulted in a two-fold increase in baseline ASMC contraction relative to control. The contractile effects exerted by IFN- priming and histamine were additive. LTD4 did not induce additional ASMC contraction in either control or IFN- primed conditions. The percentage of BrdU+ ASMCs was significantly elevated among IFN- primed cells. LTD4 did not affect the percentages of BrdU+ cells among either control or IFN- primed ASMCs. LTD4 induced prominent contraction in human ASM tissues, confirming that LTD4 activity was intact. IFN- had no effect on the CysLTR1 protein or transcript levels in ASMC. Conclusion: Cultured ASMCs lacks response to LTD4. IFN- priming increases ASMC contractility and initiates DNA synthesis but does not upregulate CysLTR1 or appear to interact with LTD4 signaling.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».