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PMID: 12349897 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Tumor necrosis factor alpha (TNF-alpha)-induced prostaglandin E2 release is mediated by the activation of cyclooxygenase-2 (COX-2) transcription via NFkappaB in human gingival fibroblasts.

Molecular and cellular biochemistry ·Vol. 238 ·No. 1-2 ·2002-09-00 ·Pages 11-8

Nakao S, Ogtata Y, Shimizu E, Yamazaki M, Furuyama S, Sugiya H

Abstract

Nuclear factor kappaB (NFkappaB) is a transcription factor and plays a key role in the expression of several genes involved in the inflammatory process. Cyclooxygenase (COX) is the key regulatory enzyme of the prostaglandin/eicosanoid synthetic pathway. COX-2 is a highly inducible enzyme by proinflammatory cytokines, of which gene expression is regulated by NFkappaB. TNF-alpha is a pro-inflammatory cytokine. In this paper, we investigated the involvement of NFkappaB on TNF-alpha-mediated prostaglandin E2 (PGE2) release and COX-2 gene expression in human gingival fibroblasts (HGF). TNF-alpha-induced PGE2 release and COX-2 mRNA accumulation in a time- and concentration-dependent manner in HGF. The results of transient transfection assays using a chimeric construct of the human COX-2 promoter (nts -1432 approximately +59) ligated to a luciferase reporter gene indicated that TNF-a stimulated the transcriptional activity approximately 1.4-fold. Gel mobility shift assays with a radiolabelled COX-2-NFkappaB oligonucleotide (nts -223 to -214) revealed an increase in the binding of nuclear proteins from TNF-alpha-stimulated HGF. The COX-2-NFKB DNA-protein complex disappeared after treatment with pyrrolidine dithiocarbamate (PDTC; an antioxidant) or herbimycin A (a tyrosine kinase inhibitor). PDTC and herbimycin A attenuated TNF-alpha-stimulated PGE2 release. These results suggest that NFkappaB transcription factor is a key regulator of COX-2 expression in TNF-alpha-induced PGE2 production, which is mediated through a tyrosine kinase pathway in HGF.

MeSH Terms

Animals Antioxidants/pharmacology Binding Sites Cattle Cells, Cultured Cyclooxygenase 2 Dinoprostone/metabolism Electrophoretic Mobility Shift Assay Enzyme Induction/drug effects Fibroblasts/drug effects,enzymology,metabolism Gingiva/cytology,drug effects,enzymology,metabolism Humans Isoenzymes/genetics Membrane Proteins NF-kappa B/metabolism Prostaglandin-Endoperoxide Synthases/genetics RNA, Messenger/genetics,metabolism Time Factors Transcription, Genetic/drug effects Tumor Necrosis Factor-alpha/pharmacology

Chemicals

Antioxidants Isoenzymes Membrane Proteins NF-kappa B RNA, Messenger Tumor Necrosis Factor-alpha Cyclooxygenase 2 PTGS2 protein, human Prostaglandin-Endoperoxide Synthases Dinoprostone

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Nakao Sumi

Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.

Ogtata Yorimasa

Shimizu Emi

Yamazaki Muneyoshi

Furuyama Shunsuke

Sugiya Hiroshi

References (37)

37 references, click to expand

Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2.
Eur J Biochem. 1994 May 1;221(3):889-97 PMID: 8181472
Involvement of NF-kappaB in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages.
FEBS Lett. 1997 Nov 24;418(1-2):175-8 PMID: 9414121
Requirement of nuclear factor kappaB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts.
J Cell Sci. 1999 Sep;112 Pt 18:3147-55 PMID: 10462530
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
Annu Rev Immunol. 2000;18:621-63 PMID: 10837071
Human cyclooxygenase-2 cDNA.
Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8 PMID: 1380156
Transforming growth factor-beta 1 regulation of bone sialoprotein gene transcription: identification of a TGF-beta activation element in the rat BSP gene promoter.
J Cell Biochem. 1997 Jun 15;65(4):501-12 PMID: 9178100
Signal transduction pathways involved in the synergistic stimulation of prostaglandin production by interleukin-1beta and tumor necrosis factor alpha in human gingival fibroblasts.
J Dent Res. 1999 Jan;78(1):61-8 PMID: 10065947
Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide: mediation through both mitogen-activated protein kinase and NF-kappaB signaling pathways in macrophages.
Biochem Pharmacol. 1997 Jul 1;54(1):87-96 PMID: 9296354
A new cationic liposome reagent mediating nearly quantitative transfection of animal cells.
Biotechniques. 1991 Apr;10(4):520-5 PMID: 1867862
Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression.
Arch Biochem Biophys. 1993 Dec;307(2):361-8 PMID: 8274023
Study of gene regulation by NF-kappa B and AP-1 in response to reactive oxygen intermediates.
Methods. 1997 Mar;11(3):301-12 PMID: 9073573
Identification of a novel response element in the rat bone sialoprotein (BSP) gene promoter that mediates constitutive and fibroblast growth factor 2-induced expression of BSP.
J Biol Chem. 2001 Feb 23;276(8):5459-66 PMID: 11087753
Interleukin-1 and tumor necrosis factor antagonists inhibit the progression of inflammatory cell infiltration toward alveolar bone in experimental periodontitis.
J Periodontol. 1998 Dec;69(12):1419-25 PMID: 9926773
COX-2 and cytosolic PLA2 mediate IL-1beta-induced cAMP production in human vascular smooth muscle cells.
Am J Physiol. 1999 Apr;276(4 Pt 2):H1369-78 PMID: 10199864
Glucocorticoid-mediated suppression of the promoter activity of the cyclooxygenase-2 gene is modulated by expression of its receptor in vascular endothelial cells.
Biochem Biophys Res Commun. 1999 Jan 19;254(2):292-8 PMID: 9918831
A comparative study of human periodontal ligament cells and gingival fibroblasts in vitro.
J Dent Res. 1988 Jan;67(1):66-70 PMID: 11039048
Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers.
Cancer Res. 1987 Nov 1;47(21):5616-9 PMID: 3664468
Expression and regulation of cyclooxygenase-2 in rat microglia.
Eur J Biochem. 1997 Feb 1;243(3):726-31 PMID: 9057838
Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
The nuclear transcription factor NF-kappaB mediates interleukin-1beta-induced expression of cyclooxygenase-2 in human myometrial cells.
Am J Obstet Gynecol. 1999 Aug;181(2):359-66 PMID: 10454683
Comparison of the characteristics of human gingival fibroblasts and periodontal ligament cells.
J Periodontol. 1995 Dec;66(12):1025-31 PMID: 8683414
Double-stranded RNA-induced inducible nitric-oxide synthase expression and interleukin-1 release by murine macrophages requires NF-kappaB activation.
J Biol Chem. 1998 Jun 12;273(24):15301-7 PMID: 9614147
Interleukin (IL)-1 and Porphyromonas gingivalis lipopolysaccharide stimulation of IL-6 production by fibroblasts derived from healthy or periodontally diseased human gingival tissue.
J Periodontol. 1999 Mar;70(3):274-82 PMID: 10225543
NF-kappa B: ten years after.
Cell. 1996 Oct 4;87(1):13-20 PMID: 8858144
Activation of NFkappaB is necessary for IL-1beta-induced cyclooxygenase-2 (COX-2) expression in human gingival fibroblasts.
Mol Cell Biochem. 2000 Jun;209(1-2):113-8 PMID: 10942208
Interleukin 1beta-secreting cells in inflamed gingival tissue of adult periodontitis patients.
Cytokine. 1999 Aug;11(8):626-33 PMID: 10433811
Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38.
Mol Cell Biol. 2001 Feb;21(3):771-80 PMID: 11154265
Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.
N Engl J Med. 1997 Apr 10;336(15):1066-71 PMID: 9091804
Structure of the human cyclo-oxygenase-2 gene.
Biochem J. 1994 Sep 15;302 ( Pt 3):723-7 PMID: 7945196
Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+ mobilization in human gingival fibroblasts primed with interleukin-1 beta.
Cell Calcium. 2001 Jun;29(6):446-52 PMID: 11352510
The cyclic AMP response element plays an essential role in the expression of the human prostaglandin-endoperoxide synthase 2 gene in differentiated U937 monocytic cells.
FEBS Lett. 1994 Aug 15;350(1):51-4 PMID: 8062923
Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells.
J Biol Chem. 1995 Dec 29;270(52):31315-20 PMID: 8537402
The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death.
Cell. 1994 Mar 25;76(6):959-62 PMID: 8137429
Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta.
Biochem Biophys Res Commun. 1997 Aug 8;237(1):28-32 PMID: 9266823
Involvement of nuclear factor kappa B in the regulation of cyclooxygenase-2 expression by interleukin-1 in rheumatoid synoviocytes.
Arthritis Rheum. 1997 Feb;40(2):226-36 PMID: 9041934
Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibits loss of tissue attachment in experimental periodontitis.
J Clin Periodontol. 2001 Mar;28(3):233-40 PMID: 11284536
Bradykinin potentiates prostaglandin E(2) release in the human gingival fibroblasts pretreated with interleukin-1beta via Ca(2+) mobilization.
Eur J Pharmacol. 2000 May 3;395(3):247-53 PMID: 10812056

Article Info

Journal

Molecular and cellular biochemistry

Abbr.

Mol Cell Biochem

ISSN

0300-8177

DOI

10.1023/a:1019927616000

Published

2002-09-00

Pages

11-8

Language

English

Region

Netherlands

NLM ID

0364456

Subset

External Links

PubMed source DOI: 10.1023/a:1019927616000 View journal details

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Tumor necrosis factor alpha (TNF-alpha)-induced prostaglandin E2 release is mediated by the activation of cyclooxygenase-2 (COX-2) transcription via NFkappaB in human gingival fibroblasts.

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