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.
Gauer
S
S
Department of Nephrology, Medical Clinic III, JW Goethe-University Frankfurt, Frankfurt, Germany. gauer@em.uni-frankfurt.de
Sichler
O
O
Obermüller
N
N
Holzmann
Y
Y
Kiss
E
E
Sobkowiak
E
E
Pfeilschifter
J
J
Geiger
H
H
Mühl
H
H
Hauser
I A
IA
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