Endo T, Ogushi F, Sone S, Ogura T, Taketani Y, Hayashi Y, Ueda N, Yamamoto S
Third Department of Internal Medicine, School of Medicine, Tokushima University, Japan.
Am J Respir Cell Mol Biol. 1995 Mar;12(3):358-65. doi: 10.1165/ajrcmb.12.3.7873203.
Because interleukin-1 beta (IL-1 beta) increases the synthesis of prostaglandin E2 (PGE2) in human lung fibroblasts, the effect of IL-1 beta on the expression of two isozymes of cyclooxygenase (cyclooxygenase-1 and -2) in human embryonic lung fibroblasts (IMR-90) was investigated in terms of three parameters (PGE2 release, cyclooxygenase activity, and mRNA). When the cells were incubated with IL-1 beta, both the PGE2 release to the culture medium and the cyclooxygenase activity in the cell lysate increased in a dose- and time-dependent manner, and both were inhibited by NS-398 (a cyclooxygenase-2-specific inhibitor). Dexamethasone and interleukin-4 (IL-4) inhibited the IL-1 beta-induced PGE2 synthesis; the former inhibited the IL-1 beta-induced cyclooxygenase activity whereas the latter failed. As analyzed by Northern blot, cyclooxygenase-1 mRNAs (3.0 Kb and 5.0 Kb) were detected with resting cells and did not increase by the addition of IL-1 beta. In contrast, the cyclooxygenase-2 mRNA (4.4 Kb) was undetectable with resting cells, but was increased dramatically up to 4 to 8 h by the addition of IL-1 beta. Dexamethasone inhibited the IL-1 beta-induced mRNA expression of cyclooxygenase-2 whereas IL-4 failed. These results indicate that IL-1 beta induces cyclooxygenase-2 rather than cyclooxygenase-1 in IMR-90 cells and this induction is responsible for the augmentation of PGE2 production stimulated with IL-1 beta. However, the inhibition of the IL-1 beta-induced PGE2 synthesis by IL-4 was not mediated by the down-regulation of cyclooxygenase-2.
由于白细胞介素-1β（IL-1β）可增加人肺成纤维细胞中前列腺素E2（PGE2）的合成，因此从三个参数（PGE2释放、环氧化酶活性和mRNA）方面研究了IL-1β对人胚肺成纤维细胞（IMR-90）中环氧化酶两种同工酶（环氧化酶-1和-2）表达的影响。当细胞与IL-1β一起孵育时，培养基中PGE2的释放和细胞裂解物中的环氧化酶活性均呈剂量和时间依赖性增加，且两者均被NS-398（一种环氧化酶-2特异性抑制剂）抑制。地塞米松和白细胞介素-4（IL-4）抑制IL-1β诱导的PGE2合成；前者抑制IL-1β诱导的环氧化酶活性，而后者则不能。通过Northern印迹分析，静息细胞可检测到环氧化酶-1 mRNA（3.0 Kb和5.0 Kb），添加IL-1β后其未增加。相反，静息细胞未检测到环氧化酶-2 mRNA（4.4 Kb），但添加IL-1β后，其在4至8小时内显著增加。地塞米松抑制IL-1β诱导的环氧化酶-2 mRNA表达，而IL-4则不能。这些结果表明，IL-1β在IMR-90细胞中诱导环氧化酶-2而非环氧化酶-1，这种诱导作用导致了IL-1β刺激的PGE2产生增加。然而，IL-4对IL-1β诱导的PGE2合成的抑制作用并非由环氧化酶-2的下调介导。
