TNF alpha Increases RANKL Expression via PGE(2)-Induced Activation ofNFATc1

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486311.do
DOI
10.3390/ijms18030495
Title
TNF alpha Increases RANKL Expression via PGE(2)-Induced Activation ofNFATc1
Description
This research was supported by the Basic Science Research Programthrough the National Research Foundation of Korea (NRF), funded by theMinistry of Education, Science, and Technology (NRF-2012R1A1A2002638).
abstract
Tumor necrosis factor alpha (TNF alpha) is known to upregulate the expression of receptor activator of NF-kappa B ligand (RANKL). We investigated the role of the calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathway in TNF alpha-induced RANKL expression in C2C12 and primary cultured mouse calvarial cells. TNF alpha-induced RANKL expression was blocked by the calcineurin/NFAT pathway inhibitors. TNF alpha increased NFAT transcriptional activity and subsequent RANKL promoter binding. Mutations in the NFAT-binding element (MT(N)) suppressed TNF alpha-induced RANKL promoter activity. TNF alpha increased prostaglandin E2 (PGE(2)) production, which in turn enhanced NFAT transcriptional activity and binding to the RANKL promoter. MT(N) suppressed PGE(2)-induced RANKL promoter activity. TNF alpha and PGE(2) increased the expression of RANKL, NFAT cytoplasmic-1 (NFATc1), cAMP response element-binding protein (CREB), and cyclooxygenase 2 (COX2); which increment was suppressed by indomethacin, a COX inhibitor. Mutations in the CRE-like element blocked PGE(2)-induced RANKL promoter activity. PGE(2) induced the binding of CREB to the RANKL promoter, whereas TNF alpha increased the binding of both CREB and NFATc1 to this promoter through a process blocked by indomethacin. The PGE(2) receptor antagonists AH6809 and AH23848 blocked TNF alpha-induced expression of RANKL, NFATc1, and CREB; transcriptional activity of NFAT; and binding of NFATc1 or CREB to the RANKL promoter. These results suggest that TNF alpha-induced RANKL expression depends on PGE(2) production and subsequent transcriptional activation/enhanced binding of NFATc1 and CREB to the RANKL promoter.
provenance
Made available in Cube on 2018-09-28T16:04:12Z (GMT). No. of bitstreams: 0
language
English
author
Park, Hyun-Jung
Baek, Kyunghwa
Baek, Jeong-Hwa
Kim, Hyung-Ryong
accessioned
2018-09-28T16:04:12Z
available
2018-09-28T16:04:12Z
issued
2017
citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(18): 3
issn
1422-0067
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486311.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274064
Jurisdiction
Rep.of Korea
Project Name
BK21 PLUS Dental Life Science
rights
openAccess
subject
TNF alpha
RANKL
PGE(2)
NFATc1
CREB
type
article


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