Pang L, Holland E, Knox A J
Division of Respiratory Medicine, City Hospital, University of Nottingham, Nottingham NG5 1PB, United Kingdom.
Am J Physiol. 1998 Aug;275(2):L322-9. doi: 10.1152/ajplung.1998.275.2.L322.
Interleukin (IL)-1beta impairs human airway smooth muscle (ASM) cell cAMP responses to isoproterenol (Iso). We investigated if bradykinin (BK) could cause a similar effect and the role of cyclooxygenase (COX) products in this event, since we have recently reported that BK, like IL-1beta, also causes COX-2 induction and prostanoid release in human ASM cells. BK pretreatment significantly attenuated Iso-induced cAMP generation in a time- and concentration-dependent manner. cAMP generation by prostaglandin (PG) E2 but not by forskolin was also impaired. The COX inhibitor indomethacin completely prevented the impairment, whereas the selective COX-2 inhibitors NS-398 and nimesulide, protein synthesis inhibitors cycloheximide and actinomycin D, and steroid dexamethasone were all partially effective. The impairment was mimicked by the B2 agonist [Tyr(Me)8]BK, the Ca2+ ionophore A-23187, and PGE2 and prevented by the B2 antagonist HOE-140, but anti-IL-1beta serum was ineffective. The results indicate that BK impairs human ASM cell responses to Iso, and the effect is largely mediated by B2 receptor-related COX product release via both COX isoforms and is independent of IL-1beta.
白细胞介素（IL）-1β会削弱人气道平滑肌（ASM）细胞对异丙肾上腺素（Iso）的环磷酸腺苷（cAMP）反应。我们研究了缓激肽（BK）是否会产生类似的效应以及环氧化酶（COX）产物在此过程中的作用，因为我们最近报道，与IL-1β一样，BK也会在人ASM细胞中诱导COX-2并释放前列腺素。BK预处理以时间和浓度依赖性方式显著减弱Iso诱导的cAMP生成。前列腺素（PG）E2而非福斯可林诱导的cAMP生成也受到损害。COX抑制剂吲哚美辛完全阻止了这种损害，而选择性COX-2抑制剂NS-398和尼美舒利、蛋白质合成抑制剂环己酰亚胺和放线菌素D以及类固醇地塞米松都只有部分效果。B2激动剂[酪氨酸（甲基）8]BK、钙离子载体A-23187和PGE2模拟了这种损害，B2拮抗剂HOE-140阻止了这种损害，但抗IL-1β血清无效。结果表明，BK会损害人ASM细胞对Iso的反应，且该效应主要由B2受体相关的COX产物通过两种COX同工型释放介导，并且与IL-1β无关。
