Endo T, Ogushi F, Sone S
Third Department of Internal Medicine, School of Medicine, Tokushima University, Japan.
J Immunol. 1996 Mar 15;156(6):2240-6.
We investigated the effects of Th2 cell-associated cytokines, IL-4, IL-10, and IL-13, on prostaglandin (PG) production by human peripheral blood monocytes (HPBM) in terms of four parameters: PGE2 synthesis; cyclooxygenase activity; protein; and mRNA of two cyclooxygenase isozymes (cyclooxygenase-1 and cyclooxygenase-2). LPS-stimulated PGE2 synthesis and cyclooxygenase activity were suppressed by IL-4, IL-10, or IL-13. Furthermore, the LPS-dependent increase of cyclooxygenase activity in HPBM was attributable to cyclooxygenase-2 because it was inhibited by NS-398 (a cyclooxygenase-2-specific inhibitor). Western and Northern blot analyses revealed that the LPS-induced increases in cyclooxygenase-2 protein and mRNA were attenuated by the addition of IL-4, IL-10, or IL-13. In contrast, cyclooxygenase-1 protein and mRNA were hardly detected in monocytes that were incubated with or without LPS in the presence or absence of IL-4, IL-10, and IL-13. These results suggest that the reduction of LPS-induced PGE2 synthesis and cyclooxygenase activity by IL-4, IL-10, and IL-13 in HPBM are mainly due to the down-regulation of cyclooxygenase-2 selectively induced by LPS. Conversely, IFN-gamma, a Th1 cell-associated cytokine, did not affect PGE2 production and cyclooxygenase activity. These data suggest a mechanism for modulation of inflammation by the anti-inflammatory Th2 cell-associated cytokines but not a Th1 cell-associated cytokine.
我们从四个参数方面研究了Th2细胞相关细胞因子白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和白细胞介素-13（IL-13）对人外周血单核细胞（HPBM）前列腺素（PG）产生的影响，这四个参数分别为：前列腺素E2（PGE2）合成；环氧化酶活性；蛋白；以及两种环氧化酶同工酶（环氧化酶-1和环氧化酶-2）的信使核糖核酸（mRNA）。IL-4、IL-10或IL-13可抑制脂多糖（LPS）刺激的PGE2合成及环氧化酶活性。此外，HPBM中环氧化酶活性的LPS依赖性增加归因于环氧化酶-2，因为它可被NS-398（一种环氧化酶-2特异性抑制剂）抑制。蛋白质免疫印迹法和Northern印迹分析显示，添加IL-4、IL-10或IL-13可减弱LPS诱导的环氧化酶-2蛋白及mRNA的增加。相反，无论有无LPS以及有无IL-4、IL-10和IL-13孵育单核细胞，均几乎检测不到环氧化酶-1蛋白及mRNA。这些结果表明，IL-4、IL-10和IL-13降低HPBM中LPS诱导的PGE2合成及环氧化酶活性，主要是由于LPS选择性诱导的环氧化酶-2下调所致。相反，Th1细胞相关细胞因子γ干扰素（IFN-γ）对PGE2产生及环氧化酶活性无影响。这些数据提示了抗炎性Th2细胞相关细胞因子而非Th1细胞相关细胞因子对炎症进行调节的一种机制。
