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-kappa B. 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-kappa B and DC maturation. Methods: DCs were isolated from bone marrow (BMOCs) 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-kappa B subunit p65. Moreover, the abundance of phosphorylated NF-kappa B inhibitor IKB alpha, of phosphorylated IKB kinase (IKK alpha/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-kappa B signaling in and maturation of DCs. Copyright (C) 2014 S. Karger AG, Basel.
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Morehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
Nagoya City Univ, Dept Integrat Anat, Grad Sch Med Sci, Nagoya, Aichi, JapanMorehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
Inoue, Koichi
Leng, Tiandong
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Morehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USAMorehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
Leng, Tiandong
Yang, Tao
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Morehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USAMorehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
Yang, Tao
Zeng, Zhao
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Morehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USAMorehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
Zeng, Zhao
Ueki, Takatoshi
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Nagoya City Univ, Dept Integrat Anat, Grad Sch Med Sci, Nagoya, Aichi, JapanMorehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
Ueki, Takatoshi
Xiong, Zhi-Gang
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Morehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USAMorehouse Sch Med, Neurosci Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA
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Nagoya City Univ, Grad Sch Med Sci, Dept Integrat Anat, Nagoya, Aichi, JapanNagoya City Univ, Grad Sch Med Sci, Dept Integrat Anat, Nagoya, Aichi, Japan
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Salker, Madhuri S.
Christian, Mark
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Christian, Mark
Steel, Jennifer H.
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Steel, Jennifer H.
Nautiyal, Jaya
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Nautiyal, Jaya
Lavery, Stuart
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Lavery, Stuart
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Trew, Geoffrey
Webster, Zoe
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Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, Embryon Stem Cell Facil, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Webster, Zoe
Al-Sabbagh, Marwa
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Al-Sabbagh, Marwa
Puchchakayala, Goverdhan
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Univ Tubingen, Inst Physiol, Tubingen, GermanyUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Puchchakayala, Goverdhan
Foeller, Michael
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Univ Tubingen, Inst Physiol, Tubingen, GermanyUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Foeller, Michael
Landles, Christian
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Landles, Christian
Sharkey, Andrew M.
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Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Sharkey, Andrew M.
Quenby, Siobhan
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Univ Hosp, Clin Sci Res Labs, Div Reprod Hlth, Warwick Med Sch, Coventry, W Midlands, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Quenby, Siobhan
Aplin, John D.
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Univ Manchester, St Marys Hosp, Maternal & Fetal Hlth Res Ctr, Manchester M13 0JH, Lancs, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Aplin, John D.
Regan, Lesley
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Regan, Lesley
Lang, Florian
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Univ Tubingen, Inst Physiol, Tubingen, GermanyUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Lang, Florian
Brosens, Jan J.
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Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
Univ Hosp, Clin Sci Res Labs, Div Reprod Hlth, Warwick Med Sch, Coventry, W Midlands, EnglandUniv London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England