Transcriptional Regulation of Human Prostaglandin-endoperoxide Synthase-2 Gene by Lipopolysaccharide and Phorbol Ester in Vascular Endothelial Cells
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There exist two distinct isozymes of prostaglandin-endoperoxide synthase (PES). PES-2 mRNA is synergistically induced by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in bovine arterial endothelial cells. On the other hand, PES-1 mRNA is constitutively expressed under these conditions. Therefore, the promoter activities of the human genes for PES-1 and -2 in bovine arterial endothelial cells were examined. The 5'-flanking region of the human PES-2 gene (nucleotides -327 to +59) showed promoter activity inducible by LPS and TPA using transient transfection analysis, whereas that of the PES-1 gene (nucleotides -1010 to +69) showed constitutive promoter activity. Destruction of both consensus sequences for the nuclear factor responsible for the interleukin-6 expression (NF-IL6) site (nucleotides -132 to -124) and the cyclic AMP response element (CRE) (nucleotides -59 to -53) of the human PES-2 gene markedly reduced the promoter activity (25%) of the PES-2 gene after combined treatment with LPS and TPA, although single destruction of the NF-IL6 site or the CRE slightly reduced the promoter activity (60 or 90%, respectively). Moreover, cotransfection experiments showed that a trans-acting factor, CCAAT enhancer binding protein delta (C/EBP delta), which binds to both the NF-IL6 site and the CRE, increased the promoter activity of the PES-2 gene mainly through the CRE. C/EBP delta mRNA was rapidly induced by LPS. Collectively, these results suggest that transcription of the PES-2 gene in vascular endothelial cells is regulated through combination of the NF-IL6 site and the CRE and that C/EBP delta functions as one of the trans-acting factors.
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Inhibition of COX-2 activity or expression by some anti-inflammatory agents is due to interference with signalling mechanisms regulating the COX-2 gene; NF-κB, C/EBP, AP-1, and CREB have been identified as regulators of COX-2 transcription.
“The inhibition of activity or expression of COX-2 by some anti-inflammatory is due to the interference with the signalling mechanisms that regulate the COX-2 gene. In this gene, four transcription factors including NF-κB, CCAAT/enhancer-binding protein (C/EBP), activator protein 1 (AP-1) and CRE-binding protein (CREB) have been identified as regulators of COX-2 transcription [22,126].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [126]
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- Authors
- Inoue, H., Yokoyama, C., Hara, S., Tone, Y., & Tanabe, T.
- Affiliations
- National Cerebral and Cardiovascular Center (JP)
- Corresponding author
- Tanabe, Tadashi
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 270
- Issue
- 42
- Pages
- 24965-24971
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2082728629
- Cited by
- 479
- References
- 37
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 10 · 2013: 11 · 2012: 11
- FWCI
- 18.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- McKnight Foundation
- Japan Science and Technology Agency
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- cyclooxygenase-2, transcriptional regulation, lipopolysaccharide, phorbol ester, phorbol myristate acetate, vascular endothelial cells, promoter activity, cyclic AMP response element, C/EBPδ, trans-acting factors, gene induction
- MeSH terms
- Cyclic AMP, Animals, Base Sequence, Cattle, DNA-Binding Proteins, Endothelium, Vascular, Gene Expression Regulation, Humans, Lipopolysaccharides, Molecular Sequence Data, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, Tetradecanoylphorbol Acetate, Transcription, Genetic, Interleukin-6, Cyclic AMP Response Element-Binding Protein
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