Prostaglandins as endogenous mediators of interleukin 1 production.
Prostaglandins as endogenous mediators of interleukin 1 production.
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DOI：
10.4049/jimmunol.136.1.186
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发表时间：
1986-01
影响因子：
4.4
通讯作者：
S. Kunkel;S. Chensue;S. Phan
中科院分区：
文献类型：
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作者：
S. Kunkel;S. Chensue;S. Phan
我们研究了花生四烯酸（AA）的环氧合酶（CO）衍生代谢产物在脂多糖（LPS）刺激小鼠腹腔巨噬细胞产生白细胞介素1（IL 1）的调节中的作用。LPS的使用被证明是一种有效的探针，因为它仅通过CO途径刺激IL 1产生和AA代谢。通过高压液相色谱法和放射免疫测定法证明了LPS刺激的巨噬细胞产生CO代谢物前列腺素E2（PGE 2）和前列腺素I2（PGI 2;以其稳定代谢物6-酮前列腺素F1 α测定）。外源性PGE 2或PGI 2的加入导致巨噬细胞IL 1产生的剂量依赖性抑制。CO通路抑制剂（吲哚美辛、吡罗昔康和布洛芬）引起LPS诱导的IL 1应答的剂量依赖性增强。这种增强与化合物作为CO抑制剂的功效直接相关。当评估巨噬细胞衍生的成纤维细胞生长因子时，发现了类似的结果。在一个很窄的剂量范围内（0.05 ~ 0.6 IL 1单位），向巨噬细胞培养物中加入外源性IL 1可引起PGE 2水平的增加。这些研究提供了详细的证据表明，通过CO途径合成的AA代谢物可以调节LPS刺激的巨噬细胞生长因子的产生。此外，我们的数据支持的概念，IL 1，与经典的激素，可以通过自我诱导的抑制剂，PGE 2调节自己的生产。
We examined the role of cyclooxygenase (CO)-derived metabolites of arachidonic acid (AA) in the regulation of interleukin 1 (IL 1) production by lipopolysaccharide (LPS)-stimulated murine resident peritoneal macrophages. The use of LPS proved to be an efficacious probe, because it stimulated both IL 1 production and AA metabolism via only the CO pathway. The production of the CO metabolites prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2; measured as its stable metabolite 6-Keto prostaglandin F1 alpha) by LPS-stimulated macrophages was demonstrated by high pressure liquid chromatography and radioimmunoassay. The addition of exogenous PGE2 or PGI2 resulted in a dose-dependent suppression of macrophage IL 1 production. Inhibitors of the CO pathway (indomethacin, piroxicam, and ibuprofen) caused a dose-dependent augmentation in the LPS-induced IL 1 response. This augmentation directly correlated with the efficacy of the compounds as CO inhibitors. Similar results were found when macrophage-derived fibroblast growth factor was assessed. The addition of exogenous IL 1 to macrophage cultures caused an increase in the levels of PGE2, over a narrow dose range (0.05 to 0.6 IL 1 units). These studies provide detailed evidence that AA metabolites synthesized via the CO pathway can modulate the production of growth factors by LPS-stimulated macrophages. In addition, our data support the concept that IL 1, as with classical hormones, can regulate its own production through a self-induced inhibitor, PGE2.