Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis.
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.
Munger
K A
KA
Center for Glomerulonephritis, Renal Division, Emory University and Veterans Administration Medical Center, Atlanta, GA 30033, USA.
Montero
A
A
Fukunaga
M
M
Uda
S
S
Yura
T
T
Imai
E
E
Kaneda
Y
Y
Valdivielso
J M
JM
Badr
K F
KF
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis; D015316:Genetic Therapy; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology*; D007975:Leukotriene B4 / Q000031:analogs & derivatives / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D007975:Leukotriene B4; C040212:leukotriene B5; D015118:Eicosapentaenoic Acid; D001093:Arachidonate 15-Lipoxygenase