Down-regulation of cyclooxygenase-2 (COX-2) by interleukin-1 receptor antagonist in human monocytes.
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.
Porreca
E
E
Departement of Internal Medicine, University of Chieti, Medical School, Italy.
Reale
M
M
Di Febbo
C
C
Di Gioacchino
M
M
Barbacane
R C
RC
Castellani
M L
ML
Baccante
G
G
Conti
P
P
Cuccurullo
F
F
D015152:Blotting, Northern; D015153:Blotting, Western; D018929:Cell Culture Techniques; D015232:Dinoprostone / Q000097:blood; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000201:enzymology / Q000276:immunology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000276:immunology
D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone