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Involvement of NF-κB in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages
- Source :
- FEBS Letters. 418:175-178
- Publication Year :
- 1997
- Publisher :
- Wiley, 1997.
-
Abstract
- We investigated the involvement of NF-kappaB in the regulation of COX-2 protein expression and prostaglandin production in LPS-stimulated J774 macrophages. Incubation of J774 cells with LPS (1 microg/ml) for 24 h caused an increase of COX-2 protein expression and accumulation of both PGE2 and 6-keto-PGF1alpha in the cell culture medium. Ammonium pyrrolidinedithiocarbamate (APDC, 0.1, 1, 10 microM) and N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK, 1, 10, 100 microM), two inhibitors of NF-kappaB activation, suppressed in a concentration-dependent manner both LPS-induced COX-2 protein expression and prostanoid generation. Moreover, APDC and TLCK both inhibited the LPS-induced increase of NF-kappaB DNA binding activity and prevented IkappaB-alpha degradation. Our results show for the first time that NF-kappaB is involved in COX-2 protein expression in LPS-stimulated J774 macrophages and suggest that inhibitors of NF-kappaB activation may represent a useful tool for the pharmacological control of inflammation.
- Subjects :
- Lipopolysaccharides
Proline
Prostaglandin
Biophysics
Inflammation
6-Ketoprostaglandin F1 alpha
Biology
Tosyllysine Chloromethyl Ketone
Biochemistry
Dinoprostone
Gene Expression Regulation, Enzymologic
NF-κB
Cell Line
chemistry.chemical_compound
Cytosol
Structural Biology
Genetics
medicine
Animals
Tosyl-lysine chloromethylketone
Molecular Biology
Incubation
Cell Nucleus
Regulation of gene expression
Macrophages
NF-kappa B
Prostanoid
Cell Biology
COX-2
Molecular biology
Ammonium pyrrolidinedithiocarbamate
Isoenzymes
Kinetics
chemistry
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Cell culture
biology.protein
lipids (amino acids, peptides, and proteins)
Cyclooxygenase
medicine.symptom
Subjects
Details
- ISSN :
- 00145793
- Volume :
- 418
- Database :
- OpenAIRE
- Journal :
- FEBS Letters
- Accession number :
- edsair.doi.dedup.....59a44792a9adb587117d1029efc8e57b