Effects of exogenous deoxyribonuclease I in collagen antibody-induced arthritis.

Autoimmune disease Cell-free DNA Chronic inflammation Deoxyribonuclease

Journal

Journal of inflammation (London, England)
ISSN: 1476-9255
Titre abrégé: J Inflamm (Lond)
Pays: England
ID NLM: 101232234

Informations de publication

Date de publication:
09 Sep 2024
Historique:
received: 06 06 2023
accepted: 19 08 2024
medline: 10 9 2024
pubmed: 10 9 2024
entrez: 9 9 2024
Statut: epublish

Résumé

Rheumatoid arthritis (RA) is associated with a high concentration of extracellular DNA (ecDNA). This could be a consequence of the inflammation, but the ecDNA could also be involved in the unknown etiopathogenesis of RA. Clearance of ecDNA is hypothesized to prevent the development of RA. This study aimed to analyze the effects of exogenous deoxyribonuclease I (DNase I) administration in an animal model of RA. The collagen antibody-induced arthritis (CAIA) model of RA was induced in adult female DBA/1J mice. CAIA mice were treated with saline or DNase I (10 mg/kg) every 12 h for the whole duration of the experiment. Arthritic scores were assessed. Paw volume and temperature were assessed using a plethysmometer and a thermal camera, respectively. Plasma ecDNA and its subcellular origin were analyzed using fluorometry and real-time PCR. DNase activity was quantified with single radial enzyme diffusion method. The CAIA model was successfully induced as proved by a higher volume, temperature and the overall arthritis score in comparison to controls. The administration of DNase I resulted in a nearly two-fold increase in serum DNase activity. Still, it did affect neither plasma ecDNA, nor the arthritis score or other measures of joint inflammation. Our results suggest that exogenous DNase I does not prevent the development of CAIA in mice. Whether this is true for other animal models of arthritis or clinical RA requires further research. EcDNA does not seem to be involved in the pathogenesis of CAIA. Additional studies are also needed to elucidate the role of ecDNA in the development of RA, focusing especially on its origin and inhibition of ecDNA release.

Sections du résumé

BACKGROUND BACKGROUND
Rheumatoid arthritis (RA) is associated with a high concentration of extracellular DNA (ecDNA). This could be a consequence of the inflammation, but the ecDNA could also be involved in the unknown etiopathogenesis of RA. Clearance of ecDNA is hypothesized to prevent the development of RA. This study aimed to analyze the effects of exogenous deoxyribonuclease I (DNase I) administration in an animal model of RA.
METHODS METHODS
The collagen antibody-induced arthritis (CAIA) model of RA was induced in adult female DBA/1J mice. CAIA mice were treated with saline or DNase I (10 mg/kg) every 12 h for the whole duration of the experiment. Arthritic scores were assessed. Paw volume and temperature were assessed using a plethysmometer and a thermal camera, respectively. Plasma ecDNA and its subcellular origin were analyzed using fluorometry and real-time PCR. DNase activity was quantified with single radial enzyme diffusion method.
RESULTS RESULTS
The CAIA model was successfully induced as proved by a higher volume, temperature and the overall arthritis score in comparison to controls. The administration of DNase I resulted in a nearly two-fold increase in serum DNase activity. Still, it did affect neither plasma ecDNA, nor the arthritis score or other measures of joint inflammation.
CONCLUSION CONCLUSIONS
Our results suggest that exogenous DNase I does not prevent the development of CAIA in mice. Whether this is true for other animal models of arthritis or clinical RA requires further research. EcDNA does not seem to be involved in the pathogenesis of CAIA. Additional studies are also needed to elucidate the role of ecDNA in the development of RA, focusing especially on its origin and inhibition of ecDNA release.

Identifiants

pubmed: 39251994
doi: 10.1186/s12950-024-00403-z
pii: 10.1186/s12950-024-00403-z
doi:

Types de publication

Journal Article

Langues

eng

Pagination

36

Subventions

Organisme : Agentúra na Podporu Výskumu a Vývoja
ID : APVV-18-0366

Informations de copyright

© 2024. The Author(s).

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Auteurs

Kristína Macáková (K)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia.

Veronika Borbélyová (V)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia.

Mária Tekeľová (M)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia.

Jakub Janko (J)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia.

Michal Pastorek (M)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia.

Richard Hokša (R)

Health Care Surveillance Authority Department, Department of Pathology, Antolská 11, 851 07 Bratislava, Slovakia.
Forensic.sk Institute of Forensic Medical Expertise, Boženy Němcovej 8, 811 01 Bratislava, Slovakia.

Norbert Moravanský (N)

Institute of Forensic Medicine, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.
Forensic.sk Institute of Forensic Medical Expertise, Boženy Němcovej 8, 811 01 Bratislava, Slovakia.

Emöke Šteňová (E)

1st Department of Internal Medicine, Faculty of Medicine, University Hospital, Comenius University, Mickiewiczova 13, 813 69 Bratislava, Slovakia.

Barbora Vlková (B)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia.

Peter Celec (P)

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia. petercelec@gmail.com.
Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia. petercelec@gmail.com.

Classifications MeSH