Source:http://linkedlifedata.com/resource/pubmed/id/15550390
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2005-2-7
|
| pubmed:abstractText |
Adenosine is an endogenous signaling molecule that is highly up-regulated in inflammatory states. Adenosine acts through the A2b receptor, a G protein-coupled receptor that couples positively to Galpha(s) and activates adenylate cyclase. This leads to cAMP-mediated electrogenic chloride secretion in intestinal epithelia. To better understand the regulation of the A2b receptor in intestinal epithelia, we studied the effects of interferon-gamma (IFN-gamma), a potent immunomodulatory cytokine, in the T84 cell line. Pretreatment of cells with 500 units/ml IFN-gamma for 12 h inhibited an adenosine-induced short circuit current (Isc) without affecting the transepithelial resistance. Under these conditions, IFN-gamma did not inhibit the protein expression or membrane recruitment of the A2b receptor, shown to be essential for its function. Interestingly, IFN-gamma inhibited cAMP levels as well as its downstream signaling pathway as shown by the inhibition of adenosine-induced phosphorylation of cAMP response element-binding protein and protein kinase A activity. Similar studies with forskolin, a direct activator of adenylate cyclase, also demonstrated inhibition of cAMP and its downstream response by IFN-gamma. However, IFN-gamma did not affect secretory responses to the calcium-dependent secretagogue carbachol or cAMP analog 8-bromo-cAMP, indicating that normal secretory responses to adequate second messengers in IFN-gamma-treated cells are achievable. Moreover, IFN-gamma inhibited the expression of adenylate cyclase isoforms 5 and 7. In conclusion, we demonstrate that IFN-gamma down-regulates adenosine-mediated signaling possibly through the direct inhibition of adenylate cyclase expression. We propose that IFN-gamma may acutely affect global cAMP-mediated responses in the intestinal epithelia, thereby decreasing secretory responses, which may consequently aggravate inflammatory processes.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A2B
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
11
|
| pubmed:volume |
280
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4048-57
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:15550390-Adenylate Cyclase,
pubmed-meshheading:15550390-Base Sequence,
pubmed-meshheading:15550390-Blotting, Western,
pubmed-meshheading:15550390-Cell Line,
pubmed-meshheading:15550390-Cell Membrane,
pubmed-meshheading:15550390-Cyclic AMP,
pubmed-meshheading:15550390-Cyclic AMP-Dependent Protein Kinase Type II,
pubmed-meshheading:15550390-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:15550390-Cytokines,
pubmed-meshheading:15550390-Dose-Response Relationship, Drug,
pubmed-meshheading:15550390-Down-Regulation,
pubmed-meshheading:15550390-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15550390-Electrophysiology,
pubmed-meshheading:15550390-Enzyme Activation,
pubmed-meshheading:15550390-Epithelium,
pubmed-meshheading:15550390-Gene Expression Regulation,
pubmed-meshheading:15550390-Humans,
pubmed-meshheading:15550390-Inflammation,
pubmed-meshheading:15550390-Interferon-gamma,
pubmed-meshheading:15550390-Intestines,
pubmed-meshheading:15550390-Molecular Sequence Data,
pubmed-meshheading:15550390-Phosphorylation,
pubmed-meshheading:15550390-Protein Isoforms,
pubmed-meshheading:15550390-Receptor, Adenosine A2B,
pubmed-meshheading:15550390-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15550390-Signal Transduction,
pubmed-meshheading:15550390-Time Factors
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and short circuit current in the intestinal epithelia by inhibiting the expression of adenylate cyclase.
|
| pubmed:affiliation |
Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|