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 CellsReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

Mediators of Inflammation - Volume 2016 2016, Article ID 9626427, 13 pages -

Research Article

Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, 14049-900 Ribeirão Preto, SP, Brazil

Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, 13045755 Campinas, SP, Brazil

Department of Pharmacology, School of Medicine of Ribeirão Preto, 14049-900 Ribeirão Preto, SP, Brazil

Received 9 March 2016; Revised 20 July 2016; Accepted 4 August 2016

Academic Editor: Constantino López-Macías

Copyright © 2016 Vanessa 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.

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.





Author: Vanessa Carregaro, Marcelo H. Napimoga, Raphael S. Peres, Luciana Benevides, Laís Amorim Sacramento, Larissa G. Pinto, Rena

Source: https://www.hindawi.com/



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