Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-κB Signaling in Dendritic Cells

被引:33
|
作者
Schmid, Evi [1 ]
Nguyen Thi Xuan [1 ,2 ]
Zahira, Naima [1 ]
Russo, Antonella [1 ]
Yang, Wenting [1 ]
Kuhl, Dietmar [3 ]
Faggio, Caterina [4 ]
Shumilina, Ekaterina [1 ]
Lang, Florian [1 ]
机构
[1] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany
[2] Vietnam Acad Sci & Technol, Inst Genome Res, Hanoi, Vietnam
[3] Univ Med Ctr Hamburg Eppendorf, Inst Mol & Cellular Cognit, Ctr Mol Neurobiol ZMNH, Hamburg, Germany
[4] Univ Messina, Dept Biol & Environm Sci, Sant Agata Di Messina, Italy
关键词
NF-kappa B; IKK alpha/beta; PI3; kinase; NDRG1; Phagocytosis; NA+/H+ EXCHANGER ACTIVITY; PROTEIN-KINASE; IL-12; PRODUCTION; ACTIVATION; EXPRESSION; RECEPTOR; MECHANISM; PATHWAYS; BETA; RELB;
D O I
10.1159/000366311
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:943 / 954
页数:12
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