TNF-α Stimulation of MCP-1 Expression Is Mediated by the Akt/PKB Signal Transduction Pathway in Vascular Endothelial Cells
Abstract
MCP-1 is expressed in a variety of cell types including vascular endothelial cells following induction by different stimuli such as tumor necrosis factor (TNF)-alpha. Although TNF-alpha stimulates MCP-1 expression and secretion, the mechanism by which TNF-alpha stimulates expression of the MCP-1 gene is not known. In this study, we examine the involvement of the phosphatidylinositol-3-OH kinase (PI3-kinase)-Akt/PKB pathway. Exposure of human umbilical vein endothelial cells (HUVECs) to TNF-alpha elicited the rapid phosphorylation of Akt/PKB. In HUVECs, wortmannin, a PI3-kinase inhibitor, inhibits TNF-alpha-mediated MCP-1 secretion at a dose-dependent manner. Constitutively active form of Akt/PKB induces transcription of the MCP-1 gene, and cotransfection of dominant negative Akt/PKB suppressed the activation of the MCP-1 promoter induced by TNF-alpha. These findings show that Akt/PKB participates in the TNF-alpha induction of MCP-1 gene transcription in endothelial cells.
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Vascular inflammation stimulates the production of chemoattractants and molecules such as monocyte chemotactic proteins and vascular cell adhesion molecule 1 in endothelium.
“Vascular inflammation stimulates the production of chemoattractants and molecules such as monocyte chemotactic proteins and vascular cell adhesion molecule 1 in endothelium [242,243,244].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [243]
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- Authors
- Murao, K., Ohyama, T., Imachi, H., Ishida, T., Cao, W. M., Namihira, H., Sato, M., Wong, N. C. W., & Takahara, J.
- Affiliations
- Kagawa University (JP)
- University of Calgary (CA)
- Corresponding author
- Murao, Koji
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 276
- Issue
- 2
- Pages
- 791-796
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1988123774
- Cited by
- 99
- References
- 24
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 8 · 2015: 7 · 2014: 2 · 2013: 6 · 2012: 5
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- TNF-α, MCP-1, Akt signaling, PI3-kinase, vascular endothelial cells, gene transcription, chemokine secretion, wortmannin, dominant-negative Akt
- MeSH terms
- Wortmannin, Androstadienes, Cells, Cultured, Endothelium, Vascular, Enzyme Inhibitors, Gene Expression Regulation, Humans, Phosphorylation, Promoter Regions, Genetic, Proto-Oncogene Proteins, Time Factors, Tumor Necrosis Factor-alpha, Signal Transduction, Protein Serine-Threonine Kinases, Chemokine CCL2, Proto-Oncogene Proteins c-akt
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