Send to

Choose Destination
See comment in PubMed Commons below
J Immunol. 2003 May 1;170(9):4578-92.

The cyclopentenone-type prostaglandin 15-deoxy-delta 12,14-prostaglandin J2 inhibits CD95 ligand gene expression in T lymphocytes: interference with promoter activation via peroxisome proliferator-activated receptor-gamma-independent mechanisms.

Author information

  • 1Dipartimento di Medicina Sperimentale e Patologia, Istituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy.


15-Deoxy-delta(12,14)-PGJ(2) (15d-PGJ(2)) is a cyclopentenone-type PG endowed with anti-inflammatory properties and produced by different cells, including those of the immune system. 15d-PGJ(2) is a natural ligand of the peroxisome proliferator-activated receptor (PPAR)-gamma nuclear receptor, but relevant PPARgamma-independent actions mediated by this prostanoid have been described. Fas (APO-1/CD95) and its ligand (Fas-L) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T cells, the Fas-Fas-L system regulates activation-induced cell death and has been implicated in diseases in which lymphocyte homeostasis is compromised. Moreover, several studies have described the pathogenic functions of Fas and Fas-L in vivo, particularly in the induction-progression of organ-specific autoimmune diseases. In this study we describe the effect of 15d-PGJ(2) on the activation of the fas-L gene in T lymphocytes. We show that 15d-PGJ(2) inhibits fas-L mRNA expression, activation-induced cell death, and fas-L promoter activity by mechanisms independent of PPARgamma and mediated by its chemically reactive cyclopentenone moiety. Our data indicate that 15d-PGJ(2) may repress fas-L activation by interfering with the expression and/or transcriptional activity of different transcription factors (early growth response types 3 and 1, NF-kappaB, AP-1, c-Myc, Nur77) whose altered balancing and transactivation may contribute for overall repression of this gene. In addition, the activation/expression of the heat shock response genes HSF-1 and HSP70 is not directly involved in the repression, and the electrophilic molecule cyclopentenone (2-cyclopenten-1-one) may reproduce the effects mediated by 15d-PGJ(2). These results suggest that modulation of Fas-L by 15d-PGJ(2) in T cells may represent an additional tool to consider for treatment of specific autoimmune and inflammatory disorders.

[PubMed - indexed for MEDLINE]
Free full text

Publication Types, MeSH Terms, Substances

Publication Types

MeSH Terms


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center