Gene expression profiling in inflammatory airway disease associated with elevated adenosine.
Adenosine has been implicated as a modulator of inflammatory processes central to asthma. However, the molecular mechanisms involved are poorly understood. We used Atlas mouse cDNA arrays to analyze differential gene expression in association with lung inflammation resulting from elevated adenosine in adenosine deaminase (ADA)-deficient mice. We report that of the 1,176 genes on the array, the expression patterns of 280 genes were consistently altered. Of these genes, the steady-state levels of 93 genes were upregulated and 29 were downregulated. We also show that lowering adenosine levels with ADA enzyme therapy has striking effects on gene expression that may be associated with resolution of pulmonary eosinophilia. In addition, we confirmed the nucleic acid and protein expression of vascular endothelial growth factor and monocyte chemoattractant protein-3, two candidate genes that may be regulated by adenosine. In conclusion, high-throughput profiling of gene expression by cDNA array hybridization has provided an overview of critical regulatory genes involved in airway inflammation in ADA-deficient mice. These mice will serve as a useful in vivo model for characterizing molecular mechanisms of adenosine-mediated lung damage.
Banerjee
Suman K
SK
Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
Young
Hays W J
HW
Volmer
Jonathan B
JB
Blackburn
Michael R
MR
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D054410:Chemokine CCL7; D016207:Cytokines; D016228:Endothelial Growth Factors / Q000032:analysis; D004804:Eosinophils / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D008222:Lymphokines / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D018945:Monocyte Chemoattractant Proteins / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000243:Adenosine Deaminase; C051409:pegademase bovine; D000241:Adenosine