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.