Int J Oral Biol.  2013 Mar;38(1):37-42.

NFATc1 and NFATc3 is Involved in the Expression of Receptor Activator of NF-kappaB Ligand in Activated T Lymphocytes

• Heo SJ
• Park HJ
• Baek JH

Abstract

Receptor activator of NF-kappaB ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as T17 cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.

Keyword

RANK ligand; T lymphocyte; NFATc1; NFATc3

MeSH Terms

Animals
Bone Resorption
Cell Line
Chromatin Immunoprecipitation
Cyclosporine
Cytokines
Interleukin-17
Ionomycin
Mice
NFATC Transcription Factors
Osteoclasts
Phorbols
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Receptors, Antigen, T-Cell
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
Cyclosporine
Cytokines
Interleukin-17
Ionomycin
NFATC Transcription Factors
Phorbols
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Receptors, Antigen, T-Cell