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J Gastroenterol Hepatol. 2013 May;28(5):823-8. doi: 10.1111/jgh.12139.

Acidic deoxycholic acid and chenodeoxycholic acid induce interleukin-8 production through p38 mitogen-activated protein kinase and protein kinase A in a squamous epithelial model.

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  • 1Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Abstract

BACKGROUND AND AIM:

Immune-mediated mucosal inflammation characterized by the production of interleukin (IL)-8 is associated with the development of gastroesophageal reflux disease. The effects of bile acids, which are major components of reflux fluid, on the production of IL-8 and related mechanisms remain unclear. This study aimed to address these questions using an esophageal stratified squamous epithelial model.

METHODS:

Normal human esophageal epithelial cells were seeded on the Transwell inserts and cultured with the air-liquid interface system to establish the model. Bile acids under different pH conditions were added to the apical compartment to examine their effects on IL-8 production and the underlying cellular signaling.

RESULTS:

Conjugated bile acids under a neutral or acidic condition did not induce IL-8 production, and unconjugated bile acids, deoxycholic acid (DCA), and chenodeoxycholic acid (CDCA) all significantly induced IL-8 production, dose- and time-dependently, only under weakly acid conditions. Inhibition of p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase A (PKA) attenuated the production of IL-8 induced by acidic DCA and CDCA. Inhibition of PKA did not block the bile acid-induced p38 MAPK activation.

CONCLUSIONS:

Compared with conjugated bile acids, the unconjugated bile acids DCA and CDCA are more likely to induce IL-8 production in vivo, especially under weakly acid conditions. This process involves two independent signaling pathways, p38 MAPK and PKA.

© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

PMID:
23425072
[PubMed - indexed for MEDLINE]
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