NFATc1 and NFATc3 is Involved in the Expression of Receptor Activator of NF-kappaB Ligand in Activated T Lymphocytes.
- Author:
Sun Jae HEO
1
;
Hyun Jung PARK
;
Jeong Hwa BAEK
Author Information
1. Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea. baekjh@snu.ac.kr
- Publication Type:Original Article
- Keywords:
RANK ligand;
T lymphocyte;
NFATc1;
NFATc3
- MeSH:
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
- From:International Journal of Oral Biology
2013;38(1):37-42
- CountryRepublic of Korea
- Language:Korean
-
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.
