Authors' contributions: Jing Shan performed experiments, analyzed data, prepared figures, and drafted the manuscript; Tadayuki Oshima designed the research, performed experiments, interpreted the results of experiments and edited the manuscript; Hirokazu Fukui and Jiro Watari interpreted the results of experiments and revised the manuscript; and Hiroto Miwa designed the research and edited the manuscript.
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
Version of Record online: 25 APR 2013
© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 5, pages 823–828, May 2013
How to Cite
Shan, J., Oshima, T., Fukui, H., Watari, J. and Miwa, H. (2013), 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. Journal of Gastroenterology and Hepatology, 28: 823–828. doi: 10.1111/jgh.12139
- Issue online: 25 APR 2013
- Version of Record online: 25 APR 2013
- Accepted manuscript online: 21 FEB 2013 02:41AM EST
- Manuscript Accepted: 20 JAN 2013
- air-liquid interface;
- chenodeoxycholic acid;
- deoxycholic acid;
- stratified epithelium
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.
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.
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.
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.