15-Deoxy-Δ12,14-prostaglandin J2 negatively regulates rankl gene expression in activated T lymphocytes

Role of NF-κB and early growth response transcription factors

Cinzia Fionda, Filomena Nappi, Mario Piccoli, Luigi Frati, Angela Santoni, Marco Cippitelli

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Receptor activator of NF-κB ligand (RANKL) and its receptor RANK are cell surface proteins abundantly expressed in bone and lymphoid tissues, whose interaction triggers different signaling pathways leading to activation and differentiation of osteoclasts, pivotal actors of the normal bone remodeling cycle. Moreover, RANKL may act as an immunomodulator, representing an important dendritic cell survival factor produced by activated T cells. A large body of research has shown that not only does the RANKL/RANK system regulate the physiology of bone development but also plays an important pathological role in bone destruction mediated by inflammatory disorders or bone metastatic tumors. 15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2) is a cyclopentenone-type PG endowed with anti-inflammatory properties and produced by different cells, including those of the immune system. Although 15d-PGJ 2 has been studied as a natural ligand of the peroxisome proliferator-activated receptor-γ nuclear receptor, relevant peroxisome proliferator-activated receptor-γ-independent actions mediated by this prostanoid have been described. In this study, we describe the effect of 15d-PGJ2 on the expression of the rankl gene in T lymphocytes. We show that 15d-PGJ2 inhibits rankl mRNA expression, protein, and rankl promoter activity by mechanisms mediated by its chemically reactive cyclopentenone moiety. Our data also indicate that 15d-PGJ2 represses rankl activation by interfering with the expression and/or activity of the transcription factors NF-κB, early growth response-2, and early growth response-3, whose altered balancing and transactivation may contribute for the repression of this gene. These results place rankl as a novel molecular target for the different immunoregulatory activities mediated by 15d-PGJ2. The physiological and pharmacological implications of these observations are discussed.

Original languageEnglish
Pages (from-to)4039-4050
Number of pages12
JournalJournal of Immunology
Volume178
Issue number7
Publication statusPublished - Apr 1 2007

Fingerprint

Early Growth Response Transcription Factors
T-Lymphocytes
Gene Expression
Peroxisome Proliferator-Activated Receptors
Bone and Bones
Ligands
Bone Remodeling
Bone Development
Immunologic Factors
Lymphoid Tissue
Osteoclasts
Cytoplasmic and Nuclear Receptors
Growth
Dendritic Cells
Transcriptional Activation
Prostaglandins
Immune System
Cell Survival
Membrane Proteins
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Immunology

Cite this

15-Deoxy-Δ12,14-prostaglandin J2 negatively regulates rankl gene expression in activated T lymphocytes : Role of NF-κB and early growth response transcription factors. / Fionda, Cinzia; Nappi, Filomena; Piccoli, Mario; Frati, Luigi; Santoni, Angela; Cippitelli, Marco.

In: Journal of Immunology, Vol. 178, No. 7, 01.04.2007, p. 4039-4050.

Research output: Contribution to journalArticle

Fionda, Cinzia ; Nappi, Filomena ; Piccoli, Mario ; Frati, Luigi ; Santoni, Angela ; Cippitelli, Marco. / 15-Deoxy-Δ12,14-prostaglandin J2 negatively regulates rankl gene expression in activated T lymphocytes : Role of NF-κB and early growth response transcription factors. In: Journal of Immunology. 2007 ; Vol. 178, No. 7. pp. 4039-4050.
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