title: Serum- and glucocorticoid-inducible kinase 1 sensitive NF-κB signaling in dendritic cells.
abstract: OBJECTIVE
  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-κB. 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-κB 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-κB subunit p65. Moreover, the abundance of phosphorylated NF-κB inhibitor IκBα, of phosphorylated IκB kinase (IKKα/β) 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.
  
  
  CONCLUSIONS
  SGK1 and NDRG1 participate in the regulation of NF-κB signaling in and maturation of DCs.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Evi
authors.initials: E
authors.lastname: Schmid
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Xuan
authors.forename: Naima
authors.initials: N
authors.lastname: Zahir
authors.forename: Antonella
authors.initials: A
authors.lastname: Russo
authors.forename: Wenting
authors.initials: W
authors.lastname: Yang
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D017931:DNA Primers; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D010587:Phagocytosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein