PMID- 25200670
OWN - NLM
STAT- MEDLINE
DCOM- 20150609
LR  - 20211203
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 34
IP  - 3
DP  - 2014
TI  - Serum- and glucocorticoid-inducible kinase 1 sensitive NF-kappaB signaling in 
      dendritic cells.
PG  - 943-54
LID - 10.1159/000366311 [doi]
AB  - BACKGROUND/AIMS: Dendritic cells (DCs), antigen-presenting cells linking innate 
      and adaptive immunity, are required for initiation of specific T cell-driven 
      immune responses. Phosphoinositide-3-kinase (PI3K) suppresses proinflammatory 
      cytokine production in DCs, which limits T helper (Th1) polarization. PI3K is in 
      part effective by downregulation of transcription factor NF-kappaB. Downstream 
      signaling elements of PI3K include serum- and glucocorticoid-inducible kinase 1 
      (SGK1) and its phosphorylation target N-myc downstream regulated gene 1 (NDRG1). 
      The present study explored whether SGK1 and NDRG1 play a role in the regulation 
      of NF-kappaB and DC-maturation. METHODS: DCs were isolated from bone marrow (BMDCs) 
      or spleen of mice lacking functional SGK1 (sgk1(-/-)) and corresponding wild type 
      mice (sgk1(+/+)). Protein abundance was determined by Western blotting. 
      Transcription was inhibited by siRNA. Abundance of maturation markers was 
      quantified by flow cytometry. FITC-dextran uptake was determined to quantify 
      phagocytosis. RESULTS: NDRG1 was similarly expressed in sgk1(+/+) and 
      sgk1(-/-)BMDCs, but SGK1-dependent phosphorylation of NDRG-1 was decreased in 
      sgk1(-/-)BMDCs. Silencing of NDRG1 in sgk1(+/+)BMDCs as compared to control empty 
      vector-treated BMDCs enhanced nuclear abundance of NF-kappaB subunit p65. Moreover, 
      the abundance of phosphorylated NF-kappaB inhibitor IkappaBalpha, of phosphorylated IkappaB 
      kinase (IKKalpha/beta) and of nuclear p65 were significantly higher in sgk1(-/-)BMDCs 
      than in sgk1(+/+)BMDCs. Expression of maturation markers, MHC II, and CD86, was 
      significantly larger and phagocytic capacity was significantly lower in sgk1(-/-) 
      than in sgk1(+/+)BMDCs. Expression of CD86 and MHCII was also significantly 
      higher in DCs isolated from the spleen of sgk1(-/-) mice than those from 
      sgk1(+/+)mice. CONCLUSION: SGK1 and NDRG1 participate in the regulation of NF-kappaB 
      signaling in and maturation of DCs.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Schmid, Evi
AU  - Schmid E
AD  - Department of Physiology, University of Tubingen, Tubingen, Germany.
FAU - Xuan, Nguyen Thi
AU  - Xuan NT
FAU - Zahir, Naima
AU  - Zahir N
FAU - Russo, Antonella
AU  - Russo A
FAU - Yang, Wenting
AU  - Yang W
FAU - Kuhl, Dietmar
AU  - Kuhl D
FAU - Faggio, Caterina
AU  - Faggio C
FAU - Shumilina, Ekaterina
AU  - Shumilina E
FAU - Lang, Florian
AU  - Lang F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140826
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (N-myc downstream-regulated gene 1 protein)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Differentiation
MH  - DNA Primers
MH  - Dendritic Cells/enzymology/immunology/*metabolism
MH  - Immediate-Early Proteins/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism
MH  - Phagocytosis
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Up-Regulation
EDAT- 2014/09/10 06:00
MHDA- 2015/06/10 06:00
CRDT- 2014/09/10 06:00
PHST- 2014/07/22 00:00 [accepted]
PHST- 2014/09/10 06:00 [entrez]
PHST- 2014/09/10 06:00 [pubmed]
PHST- 2015/06/10 06:00 [medline]
AID - 000366311 [pii]
AID - 10.1159/000366311 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2014;34(3):943-54. doi: 10.1159/000366311. Epub 2014 Aug 
      26.