Wheeler Derek S, Giuliano John S, Lahni Patrick M, Denenberg Alvin, Wong Hector R, Zingarelli Basilia
Division of Critical Care Medicine, The Kindervelt Laboratory for Critical Care Medicine Research, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Adv Pharmacol Sci. 2011;2011:691928. doi: 10.1155/2011/691928. Epub 2011 Apr 26.
Albumin appears to have proinflammatory effects in vitro. We hypothesized that albumin would induce a state of tolerance to subsequent administration of lipopolysaccharide (LPS) in vitro and in vivo. RAW264.7 and primary peritoneal macrophages were treated with increasing doses of bovine serum albumin (BSA) and harvested for NF-κB luciferase reporter assay or TNF-α ELISA. In separate experiments, RAW264.7 cells were preconditioned with 1 mg/mL BSA for 18 h prior to LPS (10 μg/mL) treatment and harvested for NF-κB luciferase reporter assay or TNF-α ELISA. Finally, C57Bl/6 mice were preconditioned with albumin via intraperitoneal administration 18 h prior to a lethal dose of LPS (60 mg/kg body wt). Blood was collected at 6 h after LPS administration for TNF-α ELISA. Albumin produced a dose-dependent and TLR-4-dependent increase in NF-κB activation and TNF-α gene expression in vitro. Albumin preconditioning abrogated the LPS-mediated increase in NF-κB activation and TNF-α gene expression in vitro and in vivo. The clinical significance of these findings remains to be elucidated.
白蛋白在体外似乎具有促炎作用。我们假设白蛋白会在体外和体内诱导对随后给予脂多糖（LPS）产生耐受状态。用递增剂量的牛血清白蛋白（BSA）处理RAW264.7细胞和原代腹腔巨噬细胞，然后收获细胞用于NF-κB荧光素酶报告基因检测或TNF-α ELISA检测。在单独的实验中，在LPS（10μg/mL）处理前18小时，用1mg/mL BSA预处理RAW264.7细胞，然后收获细胞用于NF-κB荧光素酶报告基因检测或TNF-α ELISA检测。最后，在给予致死剂量的LPS（60mg/kg体重）前18小时，通过腹腔注射用白蛋白预处理C57Bl/6小鼠。在给予LPS后6小时采集血液用于TNF-α ELISA检测。在体外，白蛋白使NF-κB激活和TNF-α基因表达呈剂量依赖性且依赖于TLR-4增加。白蛋白预处理消除了LPS介导的体外和体内NF-κB激活和TNF-α基因表达的增加。这些发现的临床意义仍有待阐明。
