Biomedical subjects

Suman K Banerjee

Publications and source records attributed to Suman K Banerjee.

3 recordsLinked to original sources

PubMed2003

Abnormal alveolar development associated with elevated adenine nucleosides.

Adenosine signaling has been characterized in various physiologic systems, but little is known about the role of adenosine signaling in lung development. Alveogenesis and microvascular maturation are the final stages in lung development in mammals. Alveogenesis in the mouse begins on Postnatal Day 5, when the process of secondary septation plays a pivotal role in the expansion of the alveolar sacs and microvascular maturation. Adenosine deaminase null mice (ADA-/-) exhibit abnormalities in alveogenesis in association with elevated lung adenosine levels. Large-scale gene expression analysis of ADA-/- lungs using oligonucleotide-based microarrays revealed novel relationships between gene expression patterns and elevated lung adenosine during the stages of alveolar maturation. Genes regulating apoptosis, proliferation, and vascular development were shown to be altered, and decreased cell proliferation in association with increased alveolar type II cell apoptosis was shown to contribute to abnormal secondary septation in these mice. ADA enzyme therapy allowed for normal patterns of apoptosis, proliferation, and alveolar development in association with prevention of adenosine elevations. These findings were correlated with the presence of adenosine receptors in the developing lung, suggesting the involvement of receptor signaling. These studies provide evidence that elevated lung adenosine can lead to abnormal alveogenesis by disrupting patterns of cell proliferation and apoptosis.

Adenine Nucleotides↗

PubMed2003

Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway.

IL-13 is an important mediator of inflammation and remodeling. We hypothesized that adenosine accumulation, alterations in adenosine receptors, and adenosine-IL-13 autoinduction are critical events in IL-13-induced pathologies. To test this, we characterized the effects of IL-13 overexpression on the levels of adenosine, adenosine deaminase (ADA) activity, and adenosine receptors in the murine lung. We also determined whether adenosine induced IL-13 in lungs from ADA-null mice. IL-13 induced an inflammatory and remodeling response that caused respiratory failure and death. During this response, IL-13 caused a progressive increase in adenosine accumulation, inhibited ADA activity and mRNA accumulation, and augmented the expression of the A1, A2B, and A3 but not the A2A adenosine receptors. ADA enzyme therapy diminished the IL-13-induced increase in adenosine, inhibited IL-13-induced inflammation, chemokine elaboration, fibrosis, and alveolar destruction, and prolonged the survival of IL-13-transgenic animals. In addition, IL-13 was strongly induced by adenosine in ADA-null mice. These findings demonstrate that adenosine and adenosine signaling contribute to and influence the severity of IL-13-induced tissue responses. They also demonstrate that IL-13 and adenosine stimulate one another in an amplification pathway that may contribute to the nature, severity, progression, and/or chronicity of IL-13 and/or Th2-mediated disorders.

Adenosine↗

PubMed2002

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.

Adenosine↗