Interleukin-5 inhibition of biliary cell chloride currents and bile flow.
Recent studies have detected significant elevations of interleukin (IL)-5 mRNA in the liver parenchyma of patients with both primary biliary cirrhosis and acute rejection after liver transplantation. In both of these disorders, intrahepatic biliary epithelial cells (BECs) are the targets of injury. We hypothesized that BECs may themselves express IL-5 receptors that may modulate key biliary functions. RNAs coding for IL-5alpha and -beta receptors were amplified by RT/PCR from a biliary cell line derived from a human cholangiocarcinoma (Mz-ChA-1) and verified by DNA sequencing. IL-5 receptor distribution was detected immunocytochemically on Mz-ChA-1 cells, immortalized murine BEC, bile duct-ligated rat liver, and isolated cholangiocytes. Patch-clamp studies on Mz-ChA-1 cells showed that IL-5 inhibits 5'-N-ethylcarboxamidoadenosine-stimulated chloride currents. Additional functional studies showed that IL-5 inhibits secretin-induced bile flow. We conclude that BECs express IL-5 receptors and that IL-5 modulates BEC chloride currents and fluid secretion. Since IL-5 has previously been associated with cholestatic liver disease, we speculate that IL-5 may contribute to liver injury through its effects on biliary secretion.
Roudebush Veterans Affairs Medical Center, Herman B. Wells Center for Pediatric Research, Riley Hospital for Children, Indiana, USA. jmcgill@lilly.com
J M
JM
McGill
M S
MS
Yen
O W
OW
Cummings
G
G
Alpini
G
G
LeSage
K E
KE
Pollok
B
B
Miller
S K
SK
Engle
A P
AP
Stansfield
D000818:Animals; D001646:Bile / Q000502:physiology*; D001659:Biliary Tract / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000096:biosynthesis / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D018123:Receptors, Interleukin / Q000378:metabolism; D053649:Receptors, Interleukin-5; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018118:Chloride Channels; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5