Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-κB Signaling in Dendritic Cells
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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-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. CONCLUSION: SGK1 and NDRG1 participate in the regulation of NF-κB signaling in and maturation of DCs.
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SGK1 and its phosphorylated target NDRG1 are involved in regulation and maturation of NF-κB signaling in antigen-presenting dendritic cells.
“SGK1 and its phosphorylated target NDRG1 are involved in the regulation and maturation of NF-κB signaling in antigen-presenting dendritic cells”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Schmid et al., 2014
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Self-citationZhao, H., Yang, J., Wang, M., Zhang, H., Zhan, Y., Cao, Z., Gu, Z., & Wang, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117019 · Cited by 6 · see citing works
Effect of Fluoride on Endocytosis and Surface Marker Expression Levels of Mouse B Cells In Vitro
Ma, H., Shi, Z., Dong, Y., Liang, R., Chen, J., Wang, J., & Wang, J. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000445651 · Cited by 5 · see citing works
Al-Hajj, S., Lemoine, R., Chadet, S., Goumard, A., Legay, L., Roxburgh, E., Héraud, A., Deluce, N. K.-N., Lamendour, L., Burlaud‐Gaillard, J., et al. (2022) · Cellular Immunology · doi:10.1016/j.cellimm.2022.104658 · Cited by 4 · see citing works
Serum and glucocorticoid-regulated kinase 1: A potential target for anticancer therapy
Mohammad, T., & Hassan, M. I. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91287-7.00013-2 · Cited by 1 · see citing works
SGK1 signaling: an important modulator of CFTR function and early immune response in mouse intestine
Muiler, C., Santos, A. K., & Ameen, N. A. (2026) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00400.2025 · Cited by 1 · see citing works
Zhu, Q., Yuan, L., Liu, S., Fung, T. S., & Liu, D. X. (2026) · Veterinary Microbiology · doi:10.1016/j.vetmic.2026.111220
- Authors
- Schmid, E., Xuan, N. T., Zahir, N., Russo, A., Yang, W., Kuhl, D., Faggio, C., Shumilina, E., & Lang, F.
- Affiliations
- University of Tübingen (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Messina (IT)
- Venue
- Cellular Physiology and Biochemistry
- Publisher
- S. Karger AG
- Published
- 2014
- Volume
- 34
- Issue
- 3
- Pages
- 943-954
- ISSN
- 1015-8987 (ISSN-L)
- 1421-9778
- OpenAlex
- W2117121496
- Cited by
- 33
- References
- 60
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 3
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Cellular Physiology and Biochemistry (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- SGK1, NDRG1, NF-κB signaling, dendritic cells, dendritic cell maturation, phosphatidylinositol 3-kinase, IκBα phosphorylation, IKKα/β, p65 nuclear translocation, MHC class II, CD86, phagocytosis, Th1 polarization, antigen presentation, bone marrow-derived dendritic cells, spleen
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, N-myc Downstream-Regulated Gene 1 Protein, Animals, Base Sequence, Cell Differentiation, Dendritic Cells, Mice, Inbred C57BL, Phagocytosis, Phosphorylation, Up-Regulation, NF-kappa B, Protein Serine-Threonine Kinases, Immediate-Early Proteins, DNA Primers, Mice, Knockout, Cell Cycle Proteins, Intracellular Signaling Peptides and Proteins, Mice, Real-Time Polymerase Chain Reaction
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