Kuroda E, Sugiura T, Zeki K, Yoshida Y, Yamashita U
Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
J Immunol. 2000 Mar 1;164(5):2386-95. doi: 10.4049/jimmunol.164.5.2386.
PGE2 has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE2 in IFN-gamma production by Staphylococcus aureus Cowan I-stimulated spleen cells from several mouse strains such as BALB/c, C3H/HeN, and C57BL/6. When spleen cells were pretreated with indomethacin (cyclooxygenase (COX)-1 and COX-2 inhibitor) or NS-398 (COX-2-specific inhibitor), S. aureus Cowan I -induced IFN-gamma production was increased more markedly in spleen cells from BALB/c mice than from C3H/HeN and C57BL/6 mouse. However, PGE2 production was not significantly different among spleen cells from three mouse strains. When various concentrations of PGE2 were exogeneously added to spleen cells, PGE2 showed a stronger suppressive effect on IFN-gamma production in spleen cells from BALB/c mice than from other strains of mice. This suppressive effect of PGE2 in BALB/c mice mainly depended on IL-12p70 production by APCs. More PGE2 binding sites were found in BALB/c spleen cells than in C3H/HeN spleen cells, indicating that the sensitivity difference to the suppressive effect of PGE2 was due to the difference of the number of PGE2 receptors. The administration of NS-398 into BALB/c mice enhanced Ag-specific IFN-gamma production, but not IL-4 production. This effect is the same as IL-12 administration in vivo. From these results, we propose that the modulation of PGE2 is important for Th1 activation via IFN-gamma and IL-12p70 production in vitro and in vivo and that PGE2 is one of the pivotal factors in the Th2-dominant immune response in BALB/c mice.
前列腺素E2（PGE2）已被证明在调节Th1和Th2型反应中起重要作用。我们研究了PGE2在金黄色葡萄球菌考恩I刺激的来自几种小鼠品系（如BALB/c、C3H/HeN和C57BL/6）的脾细胞产生干扰素-γ中的作用。当脾细胞用吲哚美辛（环氧化酶（COX）-1和COX-2抑制剂）或NS-398（COX-2特异性抑制剂）预处理时，金黄色葡萄球菌考恩I诱导的干扰素-γ产生在BALB/c小鼠的脾细胞中比在C3H/HeN和C57BL/6小鼠的脾细胞中增加得更明显。然而，三种小鼠品系的脾细胞中PGE2的产生没有显著差异。当将不同浓度的PGE2外源添加到脾细胞中时，PGE2对BALB/c小鼠脾细胞中干扰素-γ产生的抑制作用比其他小鼠品系更强。PGE2在BALB/c小鼠中的这种抑制作用主要取决于抗原呈递细胞（APC）产生的白细胞介素-12p70。在BALB/c脾细胞中发现的PGE2结合位点比在C3H/HeN脾细胞中更多，这表明对PGE2抑制作用的敏感性差异是由于PGE2受体数量的差异。向BALB/c小鼠体内注射NS-398可增强抗原特异性干扰素-γ的产生，但不增强白细胞介素-4的产生。这种作用与体内注射白细胞介素-12相同。从这些结果中，我们提出PGE2的调节对于体外和体内通过干扰素-γ和白细胞介素-12p70产生激活Th1很重要，并且PGE2是BALB/c小鼠Th2主导的免疫反应中的关键因素之一。
