Lymphotoxin-beta production following bile duct ligation: possible role for Kupffer cells.
OBJECTIVE
Lymphotoxin-beta (LT-beta) may play a role in the pathogenesis of chronic liver injury. The aim of this study was to determine in an animal model of bile duct ligation liver injury whether LT-beta expression is induced and whether Kupffer cells are an intrahepatic source of LT-beta.


METHODS
Sprague-Dawley rats were divided into two groups: one group received a single dose of GdCl (a Kupffer cell-blocking agent, 10 mg/kg i.v.), whereas the other group received saline. One day later, the groups underwent bile duct ligation or a sham operation. Liver tissue was obtained on days 1, 3, 5, and 8 for assessment of Kupffer cell numbers, early fibrogenic events and LT-beta gene expression. Kupffer cells were isolated using pronase/collagenase perfusion and centrifugal elutriation.


RESULTS
Hepatic LT-beta mRNA expression increased early following bile duct ligation. Pretreatment of bile duct-ligated animals with GdCl significantly reduced the number of Kupffer cells, delayed the rise in LT-beta expression, but had no effect on fibrogenesis. Recovery of the Kupffer cell population in these animals was accompanied by increased hepatic LT-beta expression. The LT-beta ligand and receptor were expressed by isolated normal Kupffer cells.


CONCLUSIONS
Hepatic LT-beta expression is induced early following bile duct ligation. Kupffer cells may be an intrahepatic source of LT-beta.
Lee
Clair M
CM
School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
Knight
Belinda
B
Yeoh
George C
GC
Ramm
Grant A
GA
Olynyk
John K
JK
D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D002452:Cell Count; D002478:Cells, Cultured; D007728:Kupffer Cells / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D008026:Ligation; D008099:Liver / Q000473:pathology; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053308:Lymphotoxin-beta; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011184:Postoperative Period; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism
D008024:Ligands; C505888:Ltb protein, rat; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor