Abstract
Purpose Spondyloarthritis (SpA) is a systemic inflammatory arthritis mediated mainly by interleukin (IL)-17. The vitronectin-derived bioactive peptide, VnP-16, exerts an anti-osteoporotic effect via β1 and αvβ3 integrin signaling. SpA is associated with an increased risk of osteoporosis, and we investigated the effect of VnP-16 in mice with SpA. Methods SpA was induced by curdlan in SKG ZAP-70W163C mice, which were treated with vehicle, celecoxib, VnP-16, or VnP-16+celecoxib. The clinical score, arthritis score, spondylitis score, and proinflammatory cytokine expression of the spine were evaluated by immunohistochemical staining. Type 17 helper T cell (Th17) and regulatory T cell (Treg) differentiation in the spleen was evaluated by flow cytometry and in the spine by confocal staining. Splenocyte expression of signal transducer and activator of transcription (STAT) 3 and pSTAT3 was evaluated by in vitro Western blotting. Results The clinical score was significantly reduced in the VnP16+celecoxib group. The arthritis and spondylitis scores were significantly lower in the VnP-16 and VnP16+celecoxib groups than the vehicle group. In the spine, the levels of IL-1β, IL-6, tumor necrosis factor-α, and IL-17 expression were reduced and Th17/Treg imbalance was regulated in the VnP-16 alone and VnP-16+celecoxib groups. Flow cytometry of splenocytes showed increased polarization of Tregs in the VnP-16+celecoxib group. In vitro, VnP-16 suppressed pSTAT3. Conclusions VnP-16 plus celecoxib prevented SpA progression in a mouse model by regulating the Th17/Treg imbalance and suppressing the expression of proinflammatory cytokines.
| Original language | English |
|---|---|
| Article number | e0262183 |
| Journal | PLoS ONE |
| Volume | 17 |
| Issue number | 1 January |
| DOIs | |
| State | Published - Jan 2022 |
Bibliographical note
Funding Information:Funding:Thisresearchwasfundedbyagrantfrom theKoreaHealthTechnologyR&DProjectthrough theKoreaHealthIndustryDevelopmentInstitute, fundedbytheMinistryofHealth&Welfareofthe RepublicofKorea(grantnumberHI20C1496,grant receiver:SHPark).Thefunderhadnoroleonthe studydesign,datacollectionandanalysis,decision topublish,orpreparationofthemanuscript.
Publisher Copyright:
Copyright: © 2022 Min et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.