Nakamura A, Johns E J, Imaizumi A, Yanagawa Y, Kohsaka T
Department of Paediatrics, Teikyo University School of Medicine, Tokyo, Japan.
Nephrol Dial Transplant. 2000 Dec;15(12):1928-34. doi: 10.1093/ndt/15.12.1928.
beta(2)-Adrenoceptor activation regulates tumour necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production in cultured renal cells. However, it remains uncertain whether, in vivo, the administration of beta(2)-adrenoceptor agonists regulate renal TNF-alpha and IL-6 mRNA following lipopolysaccharide (LPS) stimulation to cause endotoxaemia. This study was performed in order to evaluate the effect of beta(2)-adrenoceptor agonist on renal TNF-alpha and IL-6 production.
Four-week-old Wistar rats pre-treated with the beta(2)-adrenoceptor agonist terbutaline or formoterol, and/or the beta- and beta(2)-adrenoceptor antagonists (propanolol, ICI118,551), were injected with LPS (1 mg i.p.), and then 2, 4 or 6 h later, kidneys (cortex, medulla), spleen, thymus and plasma were collected to assay TNF-alpha and IL-6 mRNA levels and their respective protein release.
Administration of beta(2)-adrenoceptor agonists suppressed TNF-alpha mRNA expression in the whole kidney, by 61% (P<0.05), as well as plasma, spleen and thymus TNF-alpha protein and mRNA expression 2 hours after injection of LPS. On the other hand, although IL-6 levels in plasma, spleen and thymus mRNA expression were suppressed significantly by administration of beta(2)-adrenoceptor agonists, the basal- and LPS-induced IL-6 mRNA levels in the whole kidney were increased 1.6- and 1.2-fold (P<0.05), respectively, by treatment with beta(2)-adrenoceptor agonists. beta(2)-Adrenoceptor agonist suppressed LPS-induced TNF-alpha mRNA expression by 35% (P<0.05) and stimulated LPS-induced IL-6 mRNA expression by 1.5-fold (P<0.05) in the medullary region of kidney.
beta(2)-Adrenoceptor agonists down-regulate renal TNF-alpha mRNA expression following LPS-induced endotoxaemia. This effect was particularly apparent in the renal medulla. IL-6 mRNA expression in the renal medulla was up-regulated by the agonists whereas plasma, spleen and thymus IL-6 levels were completely inhibited by the agonist, which suggests the existence of tissue specific regulation of IL-6 production in the kidney by beta(2)-adrenoceptor activation.
β₂肾上腺素能受体激活可调节培养的肾细胞中肿瘤坏死因子（TNF）-α和白细胞介素-6（IL-6）的产生。然而，在体内，给予β₂肾上腺素能受体激动剂是否能调节脂多糖（LPS）刺激后导致内毒素血症时肾组织中TNF-α和IL-6的mRNA表达仍不确定。本研究旨在评估β₂肾上腺素能受体激动剂对肾组织中TNF-α和IL-6产生的影响。
对四周龄的Wistar大鼠预先给予β₂肾上腺素能受体激动剂特布他林或福莫特罗，和/或β及β₂肾上腺素能受体拮抗剂（普萘洛尔、ICI118,551），然后腹腔注射LPS（1mg），在注射后2、4或6小时，收集肾脏（皮质、髓质）、脾脏、胸腺和血浆，检测TNF-α和IL-6的mRNA水平及其各自的蛋白释放量。
给予β₂肾上腺素能受体激动剂可使LPS注射后2小时时全肾中TNF-αmRNA表达降低61%（P<0.05），同时血浆、脾脏和胸腺中TNF-α蛋白及mRNA表达也降低。另一方面，虽然给予β₂肾上腺素能受体激动剂可显著抑制血浆、脾脏和胸腺中IL-6的mRNA表达，但β₂肾上腺素能受体激动剂处理可使全肾中基础状态及LPS诱导的IL-6 mRNA水平分别升高1.6倍和1.2倍（P<0.05）。β₂肾上腺素能受体激动剂可使肾髓质区域中LPS诱导的TNF-αmRNA表达降低35%（P<0.05），并使LPS诱导的IL-6 mRNA表达升高1.5倍（P<0.05）。
β₂肾上腺素能受体激动剂可下调LPS诱导的内毒素血症后肾组织中TNF-αmRNA的表达。这种作用在肾髓质中尤为明显。肾髓质中IL-6 mRNA表达被激动剂上调，而血浆、脾脏和胸腺中IL-6水平则被激动剂完全抑制，这表明β₂肾上腺素能受体激活对肾脏中IL-6的产生存在组织特异性调节。
