Down‐regulation of cyclooxygenase‐2 (COX‐2) by interleukin‐1 receptor antagonist in human monocytes
| Autor: | Marcella Reale, Pio Conti, Giovanna Baccante, M. Di Gioacchino, Franco Cuccurullo, Renato C. Barbacane, Ettore Porreca, M.L. Castellani, C. Di Febbo |
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| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
medicine.drug_class Blotting Western Immunology Cell Culture Techniques Down-Regulation Dinoprostone Monocytes medicine Humans Immunology and Allergy RNA Messenger Northern blot Receptor biology Monocyte Receptors Interleukin-1 Interleukin Blotting Northern Receptor antagonist Molecular biology Recombinant Proteins Isoenzymes Blot Interleukin 1 receptor antagonist medicine.anatomical_structure Prostaglandin-Endoperoxide Synthases biology.protein Cyclooxygenase Interleukin-1 Research Article |
| Zdroj: | Immunology. 89:424-429 |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1046/j.1365-2567.1996.d01-753.x |
| Popis: | Cyclooxygenase (COX) is the key rate-limiting enzyme in the synthesis of prostanoids from arachidonic acid. Two isoforms of COX have been described in mammalian cells, referred to as cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is a constitutively expressed enzyme; COX-2 is an inducible enzyme that appears to be expressed in inflamed tissue and following exposure to growth factors or cytokines, such as interleukin-1 (IL-1). The aim of the present study was to test if the antagonism on the binding of IL-1 to its cell-surface receptor by human recombinant IL-1 receptor antagonist (hrIL-1ra) may control the COX mRNA expression and prostaglandin E2 (PGE2) production by human monocyte cultures. Northern blot studies showed that hrIL-ra (500 ng/ml) had a strong inhibitory effect on inducible COX activity. The effect was evident after 6 hr incubation (2.7-fold decrease of mRNA COX-2 transcripts); and about a threefold decrease at 24hr incubation. A non-significant effect was observed with COX-1 transcripts. Induced PGE2 production by monocyte cultures treated with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) was strongly inhibited in the presence of hrIL-1ra (500 ng/ml). In addition, a significant inhibition of COX-2 protein expression, as evaluated by Western blotting, was also observed. These data suggest that hrIL-1ra may be the key mediator in the down-regulation of the COX-2 inducible pathway. |
| Databáze: | OpenAIRE |
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