Theranostics 2020; 10(5):2158-2171. doi:10.7150/thno.40650 This issue Cite

Research Paper

A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients

Alexandre Mariotte1,2, Aurore De Cauwer1,2, Chrystelle Po3, Chérine Abou-Faycal1,2, Angélique Pichot1,2, Nicodème Paul1,2, Ismael Aouadi1,2, Raphael Carapito1,2, Benoit Frisch4, Cécile Macquin1,2, Emmanuel Chatelus5, Jean Sibilia1,2,5, Jean-Paul Armspach3, Seiamak Bahram1,2, Philippe Georgel1,2,✉

1. Université de Strasbourg, INSERM, ImmunoRhumatologie Moléculaire UMR_S 1109, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, F-67000 Strasbourg, France.
2. Fédération Hospitalo-Universitaire, OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, 67085 Strasbourg, France.
3. ICube, University of Strasbourg, CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), France.
4. Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, France.
5. Centre de Référence des Maladies Autoimmunes Rares, Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Citation:
Mariotte A, De Cauwer A, Po C, Abou-Faycal C, Pichot A, Paul N, Aouadi I, Carapito R, Frisch B, Macquin C, Chatelus E, Sibilia J, Armspach JP, Bahram S, Georgel P. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics 2020; 10(5):2158-2171. doi:10.7150/thno.40650. https://www.thno.org/v10p2158.htm
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Abstract

Graphic abstract

Rationale: The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1β in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1β secretion in vitro, the precise mechanisms leading to joint inflammation in gout patients are still poorly understood.

Methods: Acute urate crystal inflammation was obtained by subcutaneous injections of MSU crystals in mice. Symptoms were followed by scoring, cytokine quantification by ELISA and western blot, gene expression by RT-qPCR and RNAseq; Magnetic Resonance Imaging was also used to assess inflammation.

Results: We provide an extensive clinical, biological and molecular characterization of an acute uratic inflammation mouse model which accurately mimics human gout. We report the efficacy of topical imiquimod treatment and its impact on Interferon-dependent down modulation of Il-1β gene expression in this experimental model.

Conclusion: Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities for gout patients.


Citation styles

APA
Mariotte, A., De Cauwer, A., Po, C., Abou-Faycal, C., Pichot, A., Paul, N., Aouadi, I., Carapito, R., Frisch, B., Macquin, C., Chatelus, E., Sibilia, J., Armspach, J.P., Bahram, S., Georgel, P. (2020). A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics, 10(5), 2158-2171. https://doi.org/10.7150/thno.40650.

ACS
Mariotte, A.; De Cauwer, A.; Po, C.; Abou-Faycal, C.; Pichot, A.; Paul, N.; Aouadi, I.; Carapito, R.; Frisch, B.; Macquin, C.; Chatelus, E.; Sibilia, J.; Armspach, J.P.; Bahram, S.; Georgel, P. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics 2020, 10 (5), 2158-2171. DOI: 10.7150/thno.40650.

NLM
Mariotte A, De Cauwer A, Po C, Abou-Faycal C, Pichot A, Paul N, Aouadi I, Carapito R, Frisch B, Macquin C, Chatelus E, Sibilia J, Armspach JP, Bahram S, Georgel P. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics 2020; 10(5):2158-2171. doi:10.7150/thno.40650. https://www.thno.org/v10p2158.htm

CSE
Mariotte A, De Cauwer A, Po C, Abou-Faycal C, Pichot A, Paul N, Aouadi I, Carapito R, Frisch B, Macquin C, Chatelus E, Sibilia J, Armspach JP, Bahram S, Georgel P. 2020. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics. 10(5):2158-2171.

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