Most developing structures that express the transcription factor gene AP-2a are compromised in AP-2a mutant mouse embryos. Since the cardiac neural crest population is one prominent site of AP-2a expression, and because the neural crest is known to be required for normal cardiac morphogenesis, we have investigated the involvement of AP-2a in cardiac development. All AP-2a-deficient embryos exam...

A(2A) adenosine receptor (A(2A)AR) has potent anti-inflammatory properties, which may be important in the regulation of airway reactivity and inflammation. Inflammatory cells that possess A(2A)AR also produce nitrosative stress, which is associated with pathophysiology of asthma, so we hypothesized that A(2A)AR deficiency may lead to increased airway reactivity and inflammation through nitrosat...

The impaired renal paracrine function of dopamine in spontaneously hypertensive rats (SHR) is caused by hyperphosphorylation and desensitization of the renal D(1) dopamine receptor. Protein phosphatase 2A (PP(2A)) is critical in the regulation of G-protein-coupled receptor function. To determine whether PP(2A) expression and activity in the kidney are differentially regulated in genetic hyperte...

In several families, multiple endocrine neoplasia type 2A (MEN 2A) has been found in association with cutaneous lichen amyloidosis. It has been debated, however, whether the skin amyloidosis found in MEN 2A families, localized exclusively in the interscapular area, represents the same anomaly as that found in autosomal dominant familial cutaneous lichen amyloidosis, which is more generalized. W...

MIP-2A was recently identified as a MBP-1 interacting cellular protein. We have shown previously that MBP-1 acts as a transcriptional repressor. Functional association between MIP-2A and MBP-1 suggests that MIP-2A can act as a cofactor and relieves MBP-1-mediated transcriptional repression. In this study, we report the tissue-specific expression of MIP-2A and its role in the regulation of gene ...

In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A(2A) adenosine receptors (A(2A)Rs) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine if selective activation of A(2A)R would suppress inflammation in a rat model of glomerulonephritis. Activation of A(2A)R reduced the degree of kidney injury...

The mechanisms governing the impairment of bacterial clearance and immune function in sepsis are not known. Adenosine levels are elevated during tissue hypoxia and damage associated with sepsis. Adenosine has strong immunosuppressive effects, many of which are mediated by A(2A) receptors (A(2A)R) expressed on immune cells. We examined whether A(2A)R are involved in the regulation of immune func...

The role of monocytes/macrophages in the pathogenesis of ischemia-reperfusion injury (IRI) is unknown. We sought to determine whether activation of macrophage adenosine 2A (A(2A)) receptors (A(2A)Rs) mediates tissue protection. We subjected C57Bl/6 mice infused with clodronate [dichloromethylene bisphosphonate (Cl(2)MBP)] to IRI (32 min of ischemia followed by 24 h of reperfusion) to deplete th...

To examine the functional requirements of mengovirus 2A for virus reproduction, a series of mutants with overlapping deletions within the 2A region of mengovirus, and two chimeric constructs in which 2A is replaced either by Theiler's murine encephalomyelitis virus (TMEV) 2A or by coxsackie B3 virus (CBV3) 2Apro were generated. In vitro polyprotein synthesis showed that in both deletion mutants...

OBJECTIVE To use the mice deficient in both adenosine receptor A(2A)(A(2A)R(-/-)) and apolipoprotein E (apoE(-/-)) to investigate the role of A(2A)R in mediating the interactions of leukocytes with injured arterial walls and the formation of arterial neointima induced by a guide wire. METHODS AND RESULTS In apoE(-/-) mice, A(2A)R deficiency increased the size of the arterial neointima in inju...