| First Author | Xu Y | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 21 | Pages | 14213-20 |
| PubMed ID | 18359773 | Mgi Jnum | J:137579 |
| Mgi Id | MGI:3801252 | Doi | 10.1074/jbc.M708657200 |
| Citation | Xu Y, et al. (2008) Major histocompatibility class II transactivator expression in smooth muscle cells from A2b adenosine receptor knock-out mice: cross-talk between the adenosine and interferon-gamma signaling. J Biol Chem 283(21):14213-20 |
| abstractText | Atherosclerosis characterized by sustained inflammation and aberrant extracellular matrix alterations. Our previous investigation has defined major histocompatibility class II transactivator (CIITA) as a key factor in mediating these two processes in smooth muscle cells. Here, we demonstrate that CIITA and major histocompatibility class II expression are elevated in interferon-gamma (IFN-gamma)-treated smooth muscle cells from A2b adenosine receptor (A2bAR(-/-)) knock-out mice, as compared with wild type cells. An A2-type adenosine receptor agonist suppresses these effects of IFN-gamma in wild type cells, which can be blocked by an A2bAR-specific antagonist. We further identify that increased cellular cAMP levels are responsible for the down-regulation of CIITA expression and, hence, reduced IFN-gamma response as evidenced by the following data: 1) direct activation of adenylyl cyclase activity is both necessary and sufficient to suppress the IFN-gamma response; 2) inhibition of phosphodiesterase activity attenuates IFN-gamma induced transcription events; and 3) direct treatment with cAMP analog abrogates CIITA activation and IFN-gamma response. Therefore, our data establish possible cross-talk between the adenosine signaling through cAMP and IFN-gamma during regulation of CIITA expression. |
