IL-18 is expressed in the intercalated cell of human kidney.
We determined the cellular location of interleukin-18 (IL-18) and caspase-1 and the purinergic receptor P2X7, two proteins necessary for its activation and secretion. The mRNA and protein of IL-18 were detectable in normal human kidney by means of polymerase chain reaction (PCR), in situ hybridization, and Western blot. Immunohistochemistry located IL-18 to nephron segments containing calbinbin-D28k or aquaporin-2 that suggest location in the distal convoluted and the connecting tubule and to parts of the collecting duct. IL-18 was not detected in the thick ascending limb of Henle. Confocal microscopy showed that IL-18 was expressed in cells negative for calbindin-D28k and for aquaporin-2 but positive for the vacuolar H(+)-ATPase. This demonstrates that the intercalated cells produce IL-18. These segments were also positive for caspase-1 and P2X7 that are essential for IL-18 secretion. Our results show that IL-18 is constitutively expressed by intercalated cells of the late distal convoluted tubule, the connecting tubule, and the collecting duct of the healthy human kidney. Since IL-18 is an early component of the inflammatory cytokine cascade, its location suggests that renal intercalated cells may contribute to immediate immune response of the kidney.
Department of Nephrology, Medical Clinic III, JW Goethe-University Frankfurt, Frankfurt, Germany. gauer@em.uni-frankfurt.de
S
S
Gauer
O
O
Sichler
N
N
Obermüller
Y
Y
Holzmann
E
E
Kiss
E
E
Sobkowiak
J
J
Pfeilschifter
H
H
Geiger
H
H
Mühl
I A
IA
Hauser
D000328:Adult; D000368:Aged; D051399:Aquaporin 2 / Q000378:metabolism; D064092:Calbindin 1; D064026:Calbindins; D020170:Caspase 1 / Q000378:metabolism; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009399:Nephrons / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D051399:Aquaporin 2; C576498:CALB1 protein, human; D064092:Calbindin 1; D064026:Calbindins; D020382:Interleukin-18; C546468:P2RX7 protein, human; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D064030:S100 Calcium Binding Protein G; D020170:Caspase 1