PMID- 27852742
OWN - NLM
STAT- MEDLINE
DCOM- 20170808
LR  - 20181113
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 198
IP  - 1
DP  - 2017 Jan 1
TI  - Soluble TNF Regulates TACE via AP-2alpha Transcription Factor in Mouse Dendritic 
      Cells.
PG  - 417-427
AB  - Dendritic cells (DCs), the essential immunoregulatory and APCs, are major 
      producers of the central mediator of inflammation, soluble TNF-alpha (sTNF). sTNF is 
      generated by TNF-alpha converting enzyme (TACE) proteolytic release of the 
      transmembrane TNF (tmTNF) ectodomain. The mechanisms of TACE and sTNF regulation 
      in DCs remain elusive. This study newly defines that sTNF regulates TACE in mouse 
      DCs by engaging the AP-2alpha transcription factor. We found that the expression of 
      AP-2alpha was higher, whereas the expression and activity of TACE were lower, in 
      wild-type DCs (wtDCs) than in TNF knockout (TNFko) DCs. Exogenous sTNF rapidly 
      and simultaneously induced increases of AP-2alpha expression and decreases of TACE 
      expression and activity in wtDCs and TNFko DCs, indicating that AP-2alpha and TACE 
      are inversely dependent on sTNF and are functionally associated. To define this 
      functional association, we identified an AP-2alpha binding site in TACE promoter and 
      demonstrated, using EMSAs and chromatin immunoprecipitation assays, that AP-2alpha 
      could bind to TACE promoter in a TNF-dependent manner. Additionally, sTNF 
      simultaneously enhanced AP-2alpha expression and decreased TACE promoter luciferase 
      activity in DCs. Similarly, transfection of AP-2alpha cDNA decreased TACE promoter 
      luciferase activity, TACE expression, and TACE enzymatic activity in wtDCs or 
      TNFko DCs. In contrast, transfection of AP-2alpha small interfering RNA increased 
      TACE promoter luciferase activity, TACE expression, and TACE enzymatic activity 
      in wtDCs. These results show that TACE is a target of, and is downregulated by, 
      sTNF-induced AP-2alpha transcription factor in DCs.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Ge, Lisheng
AU  - Ge L
AD  - Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15232.
FAU - Vujanovic, Nikola L
AU  - Vujanovic NL
AD  - Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15232; vujanovicnl@upmc.edu.
AD  - Department of Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15232; and.
AD  - VA Pittsburgh Healthcare System, Pittsburgh, PA 15261.
LA  - eng
GR  - R01 DE014775/DE/NIDCR NIH HHS/United States
GR  - R01 DE017150/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20161116
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Transcription Factor AP-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (Adam17 protein, mouse)
SB  - IM
MH  - ADAM17 Protein/immunology/*metabolism
MH  - Animals
MH  - Chromatin Immunoprecipitation
MH  - Dendritic Cells/immunology/*metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Gene Expression Regulation/immunology
MH  - Immunoblotting
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Transcription Factor AP-2/immunology/*metabolism
MH  - Tumor Necrosis Factor-alpha/immunology/*metabolism
PMC - PMC5173404
MID - NIHMS826470
EDAT- 2016/11/18 06:00
MHDA- 2017/08/09 06:00
PMCR- 2018/01/01
CRDT- 2016/11/18 06:00
PHST- 2016/03/24 00:00 [received]
PHST- 2016/10/25 00:00 [accepted]
PHST- 2016/11/18 06:00 [pubmed]
PHST- 2017/08/09 06:00 [medline]
PHST- 2016/11/18 06:00 [entrez]
PHST- 2018/01/01 00:00 [pmc-release]
AID - jimmunol.1600524 [pii]
AID - 10.4049/jimmunol.1600524 [doi]
PST - ppublish
SO  - J Immunol. 2017 Jan 1;198(1):417-427. doi: 10.4049/jimmunol.1600524. Epub 2016 
      Nov 16.