Cited by 647Inflammatory mediators and NSAID effectsNF-κB Signaling PathwaysSignaling Pathways in Disease

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Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells.

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Yamamoto, Kei, Arakawa, Toshiya, Ueda, Natsuo, Yamamoto, Shozo·1995·Journal of Biological Chemistry

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Abstract

When a mouse osteoblastic cell line MC3T3-E1 was cultured in the presence of tumor necrosis factor alpha (TNF alpha), the release of prostaglandin E2 and the cyclooxygenase activity increased in a dose- and time-dependent manner. The increase of the enzyme activity was attributed mostly to the induction of cyclooxygenase-2 rather than cyclooxygenase-1 as judged by the inhibitory effect of NS398, Western blotting, and Northern blotting. In this system we attempted to elucidate the transcriptional regulation of the cyclooxygenase-2 gene. As examined by the luciferase assay, two positive regulatory regions (-186 to -131 and -512 to -385 base pairs) were found in the 5'-flanking promoter region of the mouse cyclooxygenase-2 gene in the TNF alpha-stimulated cells. The former included putative NF-IL6 (C/EBP beta) and AP2 elements, and the latter contained the NF kappa B motif. A DNA probe including the NF-IL6 and AP2 sites gave positive bands upon electrophoretic mobility shift assay using the nuclear extracts of MC3T3-E1 cells. The bands were supershifted by the addition of anti-NF-IL6 antibody but not by anti-AP2 antibody. A probe including the NF kappa B site also gave positive bands, which were supershifted by anti-NF kappa B p50 and p65 antibodies. Furthermore, when the motif of NF-IL6 or NF kappa B or both was subjected to point mutation, the luciferase activity was markedly reduced. These data suggested a potential role of both NF-IL6 and NF kappa B in the induction of cyclooxygenase-2 by TNF alpha.

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BackgroundInfluential
Acetyl-11-Keto-β-Boswellic Acid Potentiates Apoptosis, Inhibits Invasion, and Abolishes Osteoclastogenesis by Suppressing NF-κB and NF-κB-Regulated Gene Expression
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BackgroundInfluential
Prostaglandin E2 Regulates the Level and Stability of Cyclooxygenase-2 mRNA through Activation of p38 Mitogen-activated Protein Kinase in Interleukin-1β-treated Human Synovial Fibroblasts
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Zerumbone abolishes NF-κB and IκBα kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion
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Background
Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line
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Background
Cyclooxygenase (COX)-2 Inhibitor Celecoxib Abrogates TNF-Induced NF-κB Activation through Inhibition of Activation of IκBα Kinase and Akt in Human Non-Small Cell Lung Carcinoma: Correlation with Suppression of COX-2 Synthesis
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Background
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Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-κB Activity
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Authors: Yamamoto, K., Arakawa, T., Ueda, N., & Yamamoto, S.
Affiliations: Tokushima University (JP)
Corresponding author: Yamamoto, Kei
Yamamoto, Shozo
ORCID: Yamamoto, Kei
Arakawa, Toshiya
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1995-12
Volume: 270
Issue: 52
Pages: 31315-31320
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.270.52.31315
OpenAlex: W2002708977
Cited by: 647
References: 38
Citations by year: 2026: 2 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 3 · 2021: 17 · 2020: 8 · 2019: 11 · 2018: 12 · 2017: 8 · 2016: 10 · 2015: 8 · 2014: 10 · 2013: 15 · 2012: 14
FWCI: 17.65
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9116 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Japan Foundation for Applied Enzymology
Japan Research Foundation for Clinical Pharmacology
Kissei
Ono Pharmaceutical
Japan Society for the Promotion of Science
Daiichi Sankyo Company
Topics: Health Sciences › Medicine › Pharmacology (medical) › 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 › Molecular Biology › Signaling Pathways in Disease
Keywords: cyclooxygenase-2, NF-κB, NF-IL6, C/EBPβ, TNF-α, transcriptional regulation, prostaglandin E2, MC3T3-E1 cells, osteoblasts, promoter regulation, gene induction
MeSH terms: Animals, Base Sequence, DNA-Binding Proteins, Enzyme Induction, Isoenzymes, Molecular Sequence Data, Nuclear Proteins, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Tumor Necrosis Factor-alpha, NF-kappa B, 3T3 Cells, CCAAT-Enhancer-Binding Proteins, Mice

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Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells.

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