sTREM2 affects cytokine expression profiles in THP‐1 cell model.
Notice bibliographique
Résumé
Abstract Background TREM2 is an innate immune receptor expressed on myeloid cells such as microglia and macrophages and is involved in several crucial cellular response pathways including activation and inflammation. TREM2 is cleaved from cell surface by ADAM10/17 releasing as soluble TREM2 (sTREM2) and is reported to be elevated in CSF of AD patients. The relationship between inflammation and sTREM2 remains largely uncharacterized. Method THP‐1 cells were used as a myeloid model. Cells were cultured and treated with different concentrations of human recombinant sTREM2 at 2‐, 4‐, 6‐, and 8‐hour time points. LPS was used as a positive control. RT‐qPCR was used to analyze the expression of several key inflammatory and anti‐inflammatory cytokines. A commercial monoclonal rat anti‐human TREM2 IgG antibody was pre‐incubated with sTREM2 before treatment to assess its ability to mitigate effects of sTREM2 in culture. Result LPS significantly stimulated the expression of TNF‐α, IL‐1β, and IL‐6 as compared to control at all time points, and IL‐10 to a lesser extent. 0.1µg/mL sTREM2 was capable of stimulating the expression of several key pro‐inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6 post‐treatment. 0.1µg/mL sTREM2 also stimulated the expression of anti‐inflammatory cytokines IL‐10 and CCL17 post treatment. 1.0µg/mL sTREM2 was also capable of stimulating the expression of these cytokines while seemingly affecting the expression of anti‐inflammatory cytokines more consistently. Pre‐incubation of sTREM2 with monoclonal antibody was sufficient at alleviating the expression of TNF‐α, IL‐10 and CCL‐17 induced by exogenous sTREM2. However, the expression of IL‐1β and IL‐6 were amplified following either treatment with antibody alone or sTREM2+antibody. Conclusion Exogenous sTREM2 at a lower concentration (0.1 µg/mL) seems to stimulate expression of several pro‐inflammatory cytokines, while sTREM2 at both a lower (0.1 µg/mL) and a higher concentration (1µg/mL) appear to stimulate the expression of anti‐inflammatory cytokines more consistently in our myeloid cell model. Possibly indicating that different concentrations of sTREM2 may have different effects on cytokine expression profiles in the cell model. Co‐incubation of sTREM2 with a monoclonal anti‐human TREM2 antibody was sufficient to neutralize the effects of sTREM2 on inducing the expression of some cytokines but promoted others.
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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) | 0,002 | 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 ».