Diminished expression of apical sodium-dependent bile acid transporter in gallstone disease is independent of ileal inflammation.
BACKGROUND
Non-obese gallstone patients exhibit a diminished expression of apical sodium-dependent bile acid transporter (ASBT) in terminal ileum. Crohn's ileitis demonstrates a significant downregulation of this transporter.


OBJECTIVE
To test whether subclinical ileal inflammation contributes to gallstone disease.


METHODS
Biopsies from terminal ileum of female subjects with gallstone disease (n = 7), active Crohn's disease (n = 17) and controls (n = 22) were investigated. mRNA expression of ASBT, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-8, c-jun and c-fos was measured. c-jun and c-fos protein levels were determined and hematoxylin and eosin staining was applied for ileal histology.


RESULTS
ASBT expression was comparably low both in gallstone (47% of controls, p = 0.0093) and Crohn's disease (42% of controls, p = 0.0008). In gallstone disease there was a non-significant trend towards elevated TNF-alpha and IL-1beta, but all cytokines were increased in active Crohn's disease. c-jun and c-fos were slightly diminished in patients with gallstones. Neither cytokines nor transcription factors correlated significantly with ASBT. The gallstone-associated ileal biopsies exhibited no histological inflammation.


CONCLUSIONS
Although the expression of ASBT was similarly diminished in both gallstone and Crohn's disease, subclinical ileal inflammation does not appear to be relevant in gallstone patients. The mechanisms of transcriptional repression of ASBT in both diseases are apparently different.
Holzer
Arthur
A
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and Eberhard Karls University of Tübingen, Germany.
Harsch
Simone
S
Renner
Olga
O
Strohmeyer
André
A
Schimmel
Silke
S
Wehkamp
Jan
J
Fritz
Peter
P
Stange
Eduard F
EF
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D042882:Gallstones / Q000378:metabolism*; D006801:Humans; D007079:Ileitis / Q000378:metabolism* / Q000473:pathology; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D029363:Organic Anion Transporters, Sodium-Dependent; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; C071908:sodium-bile acid cotransporter