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Down‐regulation of cyclooxygenase‐2 (COX‐2) by interleukin‐1 receptor antagonist in human monocytes
Author(s) -
PORRECA E.,
REALE M.,
DI FEBBO C.,
DI GIOACCHINO M.,
BARBACANE R. C.,
CASTELLANI M. L.,
BACCANTE G.,
CONTI P.,
CUCCURULLO F.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-753.x
Subject(s) - cyclooxygenase , receptor antagonist , receptor , monocyte , medicine , arachidonic acid , prostaglandin , blot , endocrinology , prostaglandin e2 , antagonist , lipopolysaccharide , interleukin , western blot , enzyme , northern blot , prostaglandin e , biology , cytokine , messenger rna , biochemistry , gene
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 E 2 (PGE 2 ) 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 24 hr incubation. A non‐significant effect was observed with COX‐1 transcripts. Induced PGE 2 production by monocyte cultures treated with lipopolysaccharide (LPS) or interleukin‐1β (IL‐1β) 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.