T Endo, F Ogushi, S Sone, T Ogura, Y Taketani, Y Hayashi, N Ueda and S Yamamoto
Third Department of Internal Medicine, School of Medicine, Tokushima University, Japan.

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.

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