Back to Search
Start Over
Deoxycholic acid induces proinflammatory cytokine production by model oesophageal cells via lipid rafts.
- Source :
-
The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2021 Nov; Vol. 214, pp. 105987. Date of Electronic Publication: 2021 Aug 24. - Publication Year :
- 2021
-
Abstract
- The bile acid component of gastric refluxate has been implicated in inflammation of the oesophagus including conditions such as gastro-oesophageal reflux disease (GORD) and Barrett's Oesophagus (BO). Here we demonstrate that the hydrophobic bile acid, deoxycholic acid (DCA), stimulated the production of IL-6 and IL-8 mRNA and protein in Het-1A, a model of normal oesophageal cells. DCA-induced production of IL-6 and IL-8 was attenuated by pharmacologic inhibition of the Protein Kinase C (PKC), MAP kinase, tyrosine kinase pathways, by the cholesterol sequestering agent, methyl-beta-cyclodextrin (MCD) and by the hydrophilic bile acid, ursodeoxycholic acid (UDCA). The cholesterol-interacting agent, nystatin, which binds cholesterol without removing it from the membrane, synergized with DCA to induce IL-6 and IL-8. This was inhibited by the tyrosine kinase inhibitor genistein. DCA stimulated the phosphorylation of lipid raft component Src tyrosine kinase (Src). while knockdown of caveolin-1 expression using siRNA resulted in a decreased level of IL-8 production in response to DCA. Taken together, these results demonstrate that DCA stimulates IL-6 and IL-8 production in oesophageal cells via lipid raft-associated signaling. Inhibition of this process using cyclodextrins represents a novel therapeutic approach to the treatment of inflammatory diseases of the oesophagus including GORD and BO.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Barrett Esophagus metabolism
Bile Acids and Salts chemistry
Caveolin 1 metabolism
Cell Line, Tumor
Cholesterol chemistry
Cholesterol metabolism
Cytokines metabolism
Gastroesophageal Reflux metabolism
Gene Expression drug effects
Humans
Inflammation
Interleukin-6 metabolism
Interleukin-8 metabolism
NF-kappa B metabolism
Neoplasms metabolism
Phosphorylation
Signal Transduction
beta-Cyclodextrins metabolism
src-Family Kinases metabolism
Deoxycholic Acid chemistry
Esophagus drug effects
Lipids chemistry
Membrane Microdomains chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1220
- Volume :
- 214
- Database :
- MEDLINE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 34438042
- Full Text :
- https://doi.org/10.1016/j.jsbmb.2021.105987