Renal synthesis of leukaemia inhibitory factor (LIF), under normal and inflammatory conditions.
Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine that is particularly involved in nephrogenesis and repair of the extracellular matrix. Transgenic mice overexpressing LIF have mesangial proliferative glomerulonephritis. Also, during local inflammatory reactions, such as kidney graft rejection or urinary tract infections, urinary LIF excretion is enhanced. The aim of the study therefore was to study LIF production by normal and inflammatory diseased kidneys (glomerulonephritis or graft rejection), maintained in short cultures. To determine the responsibility of the kidney itself in LIF synthesis, we measured LIF secretion into the culture supernatants of human mesangial or renal tubular epithelial cells. Fragments from diseased kidneys, whether grafts or not, released more LIF than normal human kidney fragments, mesangial or renal tubular epithelial cells. However, LIF production was delayed in renal transplants compared to glomerulonephritic samples taken from untreated patients. In every case, LIF production was enhanced by interleukin 1beta (IL-1beta) and inhibited by IL-4 or dexamethasone, except in two severe rejection episodes. So, LIF appeared to respond to pro- and anti-inflammatory stimuli, in vitro and in vivo. Considering its biological effects, LIF could play a role in inflammatory renal diseases.
Morel
D S
DS
Department of Nephrology and Kidney Transplant, Hôpital Pellegrin, Bordeaux, France. delphine.morel@chu-acquitaine.fr
Taupin
J L
JL
Potier
M
M
Deminière
C
C
Potaux
L
L
Gualde
N
N
Moreau
J F
JF
D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged
D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines