Journal article
IL-1 receptor antagonist (IL-1RA) suppresses a hyper-IL-17 response-mediated bone loss in a murine experimental periodontitis
Archives of oral biology, Vol.144, pp.105555-105555
12/2022
DOI: 10.1016/j.archoralbio.2022.105555
PMID: 36191445
Abstract
We aimed to assess the role of interleukin − 1 receptor antagonist (IL-1RA) in a ligature-induced periodontal (LIP) model and the mechanism of IL-1RA in regulating the IL-17-mediated periodontal bone loss.
Periodontal bone loss was induced through the LIP model in WT and Il1ra-/- mice and measured by micro(μ) CT. Transcription of upstream IL-17 production signals and downstream targets in the ligated gingiva was compared by the real-time quantitative PCR (RT-qPCR) between WT and Il1ra-/- mice. Single-cell suspensions were prepared in gingiva and cervical lymph nodes and were analyzed by fluorescence-activated cell sorting to quantify IL-17+ cells and IL-17-secreting subpopulations. We locally delivered an anti-IL-17 neutralizing antibody to the ligated gingiva and compared the bone loss with the isotype control antibody-treated Il1ra-/- mice.
Il1ra-/- mice manifested significantly more bone loss than that of WT mice in the LIP model. Il17 and IL-17-associated transcripts (Il1b, Il6, Il23, Tgfb), Inos, Mrc1, Mmp13, and Rank were upregulated in the gingiva of Il1ra-/- mice in comparison to WT mice. Significantly more IL-17+ immune cells (CD45+IL17+) are present in the gingiva of Il1ra-/- mice with the majority of being TCR γδ T cells (CD45+IL-17+CD3+TCR γδ+) than WT mice. The anti-IL-17 neutralizing antibody treatment attenuated the alveolar bone loss in the LIP model.
IL-1RA plays a protective role in the murine LIP model by suppressing an expansion of the IL-17+ cells and preventing a hyper-IL-17 response in the gingiva.
•IL-1 receptor antagonist (IL-1RA) inhibits bone loss in experimental periodontitis.•Mice with null Il1ra manifested severe gingival inflammation.•The experimental periodontitis in Il1ra null mice is mediated by excess IL-17.•IL-1RA suppresses the IL-17 response in experimental periodontitis.
Details
- Title: Subtitle
- IL-1 receptor antagonist (IL-1RA) suppresses a hyper-IL-17 response-mediated bone loss in a murine experimental periodontitis
- Creators
- Jinmei Zhang - University of IowaAngela X. Wang - Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA, USAYafei Wu - Sichuan UniversityShaoping Zhang - Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Archives of oral biology, Vol.144, pp.105555-105555
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.archoralbio.2022.105555
- PMID
- 36191445
- ISSN
- 0003-9969
- eISSN
- 1879-1506
- Grant note
- DOI: 10.13039/100004368, name: Colgate Palmolive Co
- Language
- English
- Date published
- 12/2022
- Academic Unit
- Periodontics
- Record Identifier
- 9984367717602771
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