An in vitro model for osteoarthritis using long-cultured inflammatory human macrophages repeatedly stimulated with TLR agonists.
In vitro model
Inflammation
Macrophages
Osteoarthritis
TLR ligands
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
15 Sep 2023
15 Sep 2023
Historique:
revised:
14
08
2023
received:
27
03
2023
accepted:
14
09
2023
pubmed:
15
9
2023
medline:
15
9
2023
entrez:
15
9
2023
Statut:
aheadofprint
Résumé
Osteoarthritis (OA) is characterized by an abundance of inflammatory M1-like macrophages damaging local tissues. The search for new potential drugs for OA suffers from the lack of appropriate methods of long-lasting inflammation. Here we developed and characterized an in vitro protocol of long-lasting culture of primary human monocyte-derived macrophages differentiated with a combination of M-CSF+GM-CSF that optimally supported long-cultured macrophages (LC-Mϕs) for up to 15 days, unlike their single use. Macrophages repeatedly stimulated for 15 days with the TLR2 ligand Pam3CSK4 (LCS-Mϕs), showed sustained levels over time of IL-6, CCL2, and CXCL8, inflammatory mediators that were also detected in the synovial fluids of OA patients. Furthermore, macrophages isolated from the synovia of two OA patients showed an expression profile of inflammation-related genes similar to that of LCS-Mϕs, validating our protocol as a model of chronically activated inflammatory macrophages. Next, to confirm that these LCS-Mϕs could be modulated by anti-inflammatory compounds, we employed dexamethasone and/or celecoxib, two drugs widely used in OA treatment, that significantly inhibited the production of inflammatory mediators. This easy-to-use in vitro protocol of long-lasting inflammation with primary human macrophages could be useful for the screening of new compounds to improve the therapy of inflammatory disorders.
Identifiants
pubmed: 37713238
doi: 10.1002/eji.202350507
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350507Subventions
Organisme : European Union`s Horizon 2020
ID : MEFISTO
Organisme : European Union`s Horizon 2020
ID : 814444
Organisme : Instituto de Salud Carlos III: FTA is supported by a "Miguel Servet Grant"
ID : CP22/00106
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : AU is supported by FIRC-AIRC fellowhship for Italy
Informations de copyright
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
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