Journal article
Therapeutic treatment of arthritic mice with 15-deoxy Δ12,14-prostaglandin J2 (15d-PGJ2) ameliorates disease through the suppression of Th17 cells and the induction of CD4+CD25−FOXP3+ cells
- Abstract:
- The prostaglandin, 15-deoxy -prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4+ Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4+CD25− population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4+CD25− cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.7MB, Terms of use)
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- Publisher copy:
- 10.1155/2016/9626427
Authors
- Publisher:
- Hindawi
- Journal:
- Mediators of Inflammation More from this journal
- Volume:
- 2016
- Article number:
- 9626427
- Publication date:
- 2016-10-31
- Acceptance date:
- 2016-08-04
- DOI:
- EISSN:
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1466-1861
- ISSN:
-
0962-9351
- Pmid:
-
27872515
- Language:
-
English
- Pubs id:
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pubs:687571
- UUID:
-
uuid:35cbcf0a-c251-4642-a281-c6fe1a87f297
- Local pid:
-
pubs:687571
- Source identifiers:
-
687571
- Deposit date:
-
2018-11-15
- ARK identifier:
Terms of use
- Copyright holder:
- Carregaro et al
- Copyright date:
- 2016
- Notes:
- Copyright © 2016 Carregaro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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