The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Genetic Analysis of the Role of the PI3K-Akt Pathway in Lipopolysaccharide-Induced Cytokine and Tissue Factor Gene Expression in Monocytes/Macrophages
Open accessAbstract
LPS stimulation of monocytes/macrophages induces the expression of genes encoding proinflammatory cytokines and the procoagulant protein, tissue factor. Induction of these genes is mediated by various signaling pathways, including mitogen-activated protein kinases, and several transcription factors, including Egr-1, AP-1, ATF-2, and NF-κB. We used a genetic approach to determine the role of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway in the regulation of LPS signaling and gene expression in isolated macrophages and in mice. The PI3K-Akt pathway is negatively regulated by the phosphatase and tensin homologue (PTEN). We used peritoneal exudate cells from Pik3r1-deficient mice, which lack the p85α regulatory subunit of PI3K and have reduced PI3K activity, and peritoneal macrophages from PTENflox/flox/LysMCre mice (PTEN−/−), which have increased Akt activity. Analysis of LPS signaling in Pik3r1−/− and PTEN−/− cells indicated that the PI3K-Akt pathway inhibited activation of the ERK1/2, JNK1/2, and p38 mitogen-activated protein kinases and reduced the levels of nuclear Egr-1 protein and phosphorylated ATF-2. Modulating the PI3K-Akt pathway did not affect LPS-induced degradation of IκBα or NF-κB nuclear translocation. LPS induction of TNF-α, IL-6, and tissue factor gene expression was increased in Pik3r1−/− peritoneal exudate cells and decreased in PTEN−/− peritoneal macrophages compared with wild-type (WT) cells. Furthermore, LPS-induced inflammation and coagulation were enhanced in WT mice containing Pik3r1−/− bone marrow compared with WT mice containing WT bone marrow and in mice lacking the p85α subunit in all cells. Taken together, our results indicate that the PI3K-Akt pathway negatively regulates LPS signaling and gene expression in monocytes/macrophages.
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Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
LPS induction of gene expression in human monocytes
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Self-citationConditional gene targeting in macrophages and granulocytes using LysMcre mice
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PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention
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Self-citationEndotoxin signal transduction in macrophages
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Differentiation Stage-Specific Inhibition of the Raf-MEK-ERK Pathway by Akt
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Akt Phosphorylates and Negatively Regulates Apoptosis Signal-Regulating Kinase 1
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Cited by
Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization
Vergadi, E., Ieronymaki, E., Lyroni, K., Vaporidi, K., & Tsatsanis, C. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601515 · Cited by 1,148
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The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs
Androulidaki, A., Iliopoulos, D., Arranz, A., Doxaki, C., Schworer, S., Zacharioudaki, V., Margioris, A. N., Tsichlis, P. N., & Tsatsanis, C. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.024 · Cited by 581
Chen, X., Tang, J., Shuai, W., Meng, J., Feng, J., & Han, Z. (2020) · Inflammation Research · doi:10.1007/s00011-020-01378-2 · Cited by 423
TLR4/MyD88/PI3K interactions regulate TLR4 signaling.
Laird, M. H. W., Rhee, S. H., Perkins, D. J., Medvedev, A. E., Piao, W., Fenton, M. J., & Vogel, S. N. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208763 · Cited by 342
Metadata
- Authors
- Luyendyk, J. P., Schabbauer, G. A., Tencati, M., Holscher, T., Pawlinski, R., & Mackman, N.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-03
- Volume
- 180
- Issue
- 6
- Pages
- 4218-4226
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1861384455
- Cited by
- 273
- References
- 46
- FWCI
- 6.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Luyendyk, J. P., Schabbauer, G. A., Tencati, M., Holscher, T., Pawlinski, R., & Mackman, N. (2008). Genetic Analysis of the Role of the PI3K-Akt Pathway in Lipopolysaccharide-Induced Cytokine and Tissue Factor Gene Expression in Monocytes/Macrophages. The Journal of Immunology. https://doi.org/10.4049/jimmunol.180.6.4218
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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