Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.
BACKGROUND
To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA.


METHODS
Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7).


RESULTS
Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC.


CONCLUSIONS
The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.
Sakisaka
S
S
Second Department of Medicine, Kurume University School of Medicine, Japan.
Koga
H
H
Sasatomi
K
K
Ohishi
M
M
Kawaguchi
T
T
Harada
M
M
Taniguchi
E
E
Uchimura
Y
Y
Ueno
T
T
Sata
M
M
Tanikawa
K
K
D000328:Adult; D000368:Aged; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D015209:Cholangitis, Sclerosing / Q000188:drug therapy / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014452:Ubiquitins / Q000032:analysis / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D018840:HSP70 Heat-Shock Proteins; D014452:Ubiquitins; D014580:Ursodeoxycholic Acid