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.
Vanessa CarregaroMarcelo Henrique NapimogaRaphael S PeresLuciana BenevidesLaís Amorim SacramentoLarissa G PintoRenata GrespanThiago M CunhaJoão Santana SilvaFernando de Queiroz CunhaPublished in: Mediators of inflammation (2016)
The prostaglandin, 15-deoxy Δ12,14-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.
Keyphrases
- rheumatoid arthritis
- induced apoptosis
- regulatory t cells
- cell cycle arrest
- lymph node
- high fat diet induced
- oxidative stress
- single cell
- disease activity
- poor prognosis
- chronic pain
- signaling pathway
- cell death
- early stage
- cell proliferation
- diabetic rats
- dendritic cells
- bone marrow
- immune response
- mesenchymal stem cells
- adipose tissue
- neoadjuvant chemotherapy
- rectal cancer
- systemic lupus erythematosus
- long non coding rna
- smoking cessation
- idiopathic pulmonary fibrosis
- radiation therapy
- newly diagnosed