PRODUCTION OF PGE(2) BY BOVINE CULTURED AIRWAY SMOOTH-MUSCLE CELLS AND ITS INHIBITION BY CYCLOOXYGENASE INHIBITORS
PRODUCTION OF PGE(2) BY BOVINE CULTURED AIRWAY SMOOTH-MUSCLE CELLS AND ITS INHIBITION BY CYCLOOXYGENASE INHIBITORS
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DOI：
10.1111/j.1476-5381.1994.tb14840.x
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发表时间：
1994-04-01
影响因子：
7.3
通讯作者：
KNOX, A
中科院分区：
文献类型：
--
作者：
DELAMERE, F;HOLLAND, E;KNOX, A
前列腺素E2（PGE 2）被认为是气道炎症过程的重要抑制性调节剂。它抑制炎症细胞功能和胆碱能神经传递在体外和角色已被假定在体内的难治性和利尿剂，速尿的作用机制。2生产的PGE 2牛培养的气道平滑肌细胞已在一系列条件下进行了研究。在一定浓度范围内（10（-7）-10（-4）M）评估环氧合酶抑制剂（氟比洛芬、吲哚美辛、乙酰水杨酸）对血清诱导的PGE 2产生的影响。3在对照威尔斯孔中，不同动物细胞中血清刺激的PGE 2产生范围为350至800 ng PGE，ml-1。所有三种环氧合酶抑制剂抑制PGE 2的产生，其效力顺序为氟比洛芬>吲哚美辛>乙酰水杨酸。对氟比洛芬、吲哚美辛和乙酰水杨酸的对数IC 50值分别为-6.24、-5.23和-3.50。4花生四烯酸（10（-5）M）或加入促炎介质刺激PGE 2的产生，缓激肽（10（-8）-10（-5）M）。5用5溴脱氧尿苷（BRDU）（10（-4）M）孵育细胞24小时以阻止DNA合成不改变响应血清的PGE 2产生，提示其本身不是增殖的功能。6我们的研究提示气道平滑肌可能是PGE 2的重要来源。PGE 2的产生可能是气道平滑肌细胞负性调节气道炎症的一种新的反馈机制。环氧合酶抑制剂的不同效力可以解释这些药物在最近的哮喘研究中的对比效果。
1 Prostaglandin E2 (PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. It inhibits inflammatory cell function and cholinergic neurotransmission in vitro and roles have been postulated in vivo in refractoriness and in the mechanism of action of the diuretic agent, frusemide.2 The production of PGE2 by bovine cultured airway smooth muscle cells has been studied under a range of conditions. The effects of cyclo-oxygenase inhibitors (flurbiprofen, indomethacin, acetyl salicylic acid) on serum-induced production of PGE2 were assessed over a range of concentrations (10(-7)-10(-4) M).3 Serum-stimulated production of PGE2 in control wells ranged from 350 to 800 ng PGE, ml-1 in cells from different animals. All three cyclo-oxygenase inhibitors inhibited PGE2 production with an order of potency, flurbiprofen > indomethacin > acetyl salicylic acid. Log IC50 values were - 6.24 for flurbiprofen, - 5.23 for indomethacin and - 3.50 for acetyl salicylic acid.4 PGE2 Production was stimulated by arachidonic acid (10(-5) M) or addition of the proinflammatory mediator, bradykinin (10(-8)-10(-5) M).5 Incubation of cells for 24 h with 5 bromo deoxyuridine (BRDU) (10(-4) M) to prevent DNA synthesis did not alter PGE2 production in response to serum, suggesting that it was not a function of proliferation per se.6 Our study suggests that airway smooth muscle may be an important source of PGE2. Production of PGE2 may be a novel feedback mechanism whereby airway smooth muscle cells can negatively modulate airways inflammation. The differing potencies of the cyclo-oxygenase inhibitors may explain the contrasting effect of these drugs in recent studies in asthma.