Munger K A, Montero A, Fukunaga M, Uda S, Yura T, Imai E, Kaneda Y, Valdivielso J M, Badr K F
Center for Glomerulonephritis, Renal Division, Emory University and Veterans Administration Medical Center, Atlanta, GA 30033, USA.
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13375-80. doi: 10.1073/pnas.96.23.13375.
The human 15-lipoxygenase (15-LO) gene was transfected into rat kidneys in vivo via intra-renal arterial injection. Three days later, acute (passive) or accelerated forms of antiglomerular basement membrane antibody-mediated glomerulonephritis were induced in transfected and nontransfected or sham-transfected controls. Studies of glomerular functions (filtration and protein excretion) and ex vivo glomerular leukotriene B(4) biosynthesis at 3 hr, and up to 4 days, after induction of nephritis revealed preservation or normalization of these parameters in transfected kidneys that expressed human 15-LO mRNA and mature protein, but not in contralateral control kidneys or sham-transfected animals. The results provide in vivo-derived data supporting a direct anti-inflammatory role for 15-LO during immune-mediated tissue injury.
通过肾动脉内注射将人15-脂氧合酶(15-LO)基因体内转染至大鼠肾脏。三天后,在转染和未转染或假转染的对照中诱导抗肾小球基底膜抗体介导的肾小球肾炎的急性(被动)或加速形式。在诱发肾炎后3小时直至4天,对肾小球功能(滤过和蛋白质排泄)以及离体肾小球白三烯B4生物合成的研究表明,在表达人15-LO mRNA和成熟蛋白的转染肾脏中,这些参数得以保留或恢复正常,而在对侧对照肾脏或假转染动物中则不然。这些结果提供了源自体内的数据,支持15-LO在免疫介导的组织损伤中具有直接抗炎作用。