Interleukin-5 inhibition of biliary cell chloride currents and bile flow

Recent studies have detected significant elevations of interleukin (IL)-5 m RNA in the liver parenchyma of patients with both primary biliary cirrhosis and acute rejection after liver transplantation. In both of these disorder s, intrahepatic biliary epithelial cells (BECs) are the targets of injury. We hypothesized that BECs may themselves express IL-5 receptors that may mo dulate key biliary functions. RNAs coding for IL-5 alpha and -beta receptor s were amplified by RT/PCR from a biliary cell line derived from a human ch olangiocarcinoma (Mz-ChA-1) and verified by DNA sequencing. IL-5 receptor d istribution was detected immunocytochemically on Mz-ChA-1 cells, immortaliz ed murine BEC, bile duct-ligated rat liver, and isolated cholangiocytes. Pa tch-clamp studies on Mz-ChA-1 cells showed that IL-5 inhibits 5'-N-ethylcar boxamidoadenosine- stimulated chloride currents. Additional functional stud ies 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 a nd fluid secretion. Since IL-5 has previously been associated with cholesta tic liver disease, we speculate that IL-5 may contribute to liver injury th rough its effects on biliary secretion.