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J Biol Chem. 2008 May 23;283(21):14213-20. doi: 10.1074/jbc.M708657200. Epub 2008 Mar 21.

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.

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Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.


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.

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