Porreca E, Reale M, Di Febbo C, Di Gioacchino M, Barbacane R C, Castellani M L, Baccante G, Conti P, Cuccurullo F
Departement of Internal Medicine, University of Chieti, Medical School, Italy.
Immunology. 1996 Nov;89(3):424-9. doi: 10.1046/j.1365-2567.1996.d01-753.x.
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.
环氧化酶（COX）是从花生四烯酸合成前列腺素的关键限速酶。在哺乳动物细胞中已描述了两种COX同工型，分别称为环氧化酶-1（COX-1）和环氧化酶-2（COX-2）。COX-1是一种组成型表达的酶；COX-2是一种诱导型酶，似乎在炎症组织中以及在暴露于生长因子或细胞因子（如白细胞介素-1（IL-1））后表达。本研究的目的是测试人重组IL-1受体拮抗剂（hrIL-1ra）对IL-1与其细胞表面受体结合的拮抗作用是否可以控制人单核细胞培养物中COX mRNA表达和前列腺素E2（PGE2）的产生。Northern印迹研究表明，hrIL-ra（500 ng/ml）对诱导型COX活性有强烈的抑制作用。孵育6小时后效果明显（COX-2 mRNA转录物减少2.7倍）；孵育24小时时减少约三倍。COX-1转录物未观察到显著影响。在存在hrIL-1ra（500 ng/ml）的情况下，用脂多糖（LPS）或白细胞介素-1β（IL-1β）处理的单核细胞培养物诱导的PGE2产生受到强烈抑制。此外，通过蛋白质印迹评估，还观察到COX-2蛋白表达的显著抑制。这些数据表明，hrIL-1ra可能是COX-2诱导途径下调的关键介质。
