Lacroix S, Rivest S
Laboratory of Molecular Endocrinology, CHUL Research Center and Laval University, Sainte-Foy, Québec, Canada.
J Neurochem. 1998 Feb;70(2):452-66. doi: 10.1046/j.1471-4159.1998.70020452.x.
The aim of this study was to investigate the influence of the acute-phase response and the proinflammatory cytokines on the transcription of the genes encoding the limiting enzymes for the production of prostaglandins, cyclooxygenase (COX)-1 and COX-2, in the rat brain. The bacterial endotoxin lipopolysaccharide (intravenous and intraperitoneal) and turpentine (intramuscular) were used as different models of inflammation in adult male rats. Animals were also killed at various times after intravenous administration of interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6, and mRNAs encoding COX-1 and COX-2 were assayed by in situ hybridization histochemistry. A profound transcriptional activation of the gene encoding COX-2 was detected over blood vessels of the entire brain microvasculature, choroid plexus, and leptomeninges of lipopolysaccharide-challenged rats. Injection of the endotoxin intravenously also increased COX-2 gene expression within parvocellular division of the hypothalamic paraventricular nucleus. It is interesting that intramuscular turpentine injection stimulated transcription of COX-2 along endothelium of brain capillaries, and the signal of this transcript paralleled the inflammation of the left hind limb. A robust COX-2 mRNA signal was detected rapidly in the brain microvessels of interleukin-1beta-injected rats, whereas tumor necrosis factor-alpha administration caused a modest but significant induction of this transcript. In contrast, intravenous injection of interleukin-6 did not alter genetic expression of COX-2, and none of the above described models affected the synthesis of COX-1 gene in the rat brain. These results indicate that specific cell populations, in particular vascular- and/or perivascular-associated cells, are responsible for the central production of prostaglandins during systemic inflammation, and circulating interleukin-1beta is likely to be a potent mediator of this response.
本研究旨在探讨急性期反应和促炎细胞因子对大鼠脑中编码前列腺素生成限速酶的基因——环氧化酶（COX）-1和COX-2转录的影响。细菌内毒素脂多糖（静脉内和腹膜内注射）和松节油（肌肉内注射）被用作成年雄性大鼠不同的炎症模型。在静脉注射白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6后的不同时间点处死动物，并通过原位杂交组织化学法检测编码COX-1和COX-2的mRNA。在脂多糖攻击的大鼠的整个脑微血管、脉络丛和软脑膜的血管上检测到编码COX-2的基因的显著转录激活。静脉注射内毒素也增加了下丘脑室旁核小细胞部内COX-2基因的表达。有趣的是，肌肉内注射松节油刺激了脑毛细血管内皮细胞COX-2的转录，并且该转录本的信号与左后肢的炎症平行。在注射白细胞介素-1β的大鼠的脑微血管中迅速检测到强烈的COX-2 mRNA信号，而给予肿瘤坏死因子-α导致该转录本有适度但显著的诱导。相反，静脉注射白细胞介素-6并未改变COX-2的基因表达，并且上述模型均未影响大鼠脑中COX-1基因的合成。这些结果表明，特定的细胞群体，特别是血管和/或血管周围相关细胞，在全身炎症期间负责脑中前列腺素的产生，并且循环中的白细胞介素-1β可能是这种反应的有效介质。
