TY - JOUR
T1 - Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway
AU - Blackburn, Michael R.
AU - Lee, Chun G.
AU - Young, Hays W.J.
AU - Zhu, Zhou
AU - Chunn, Janci L.
AU - Kang, Min Jong
AU - Banerjee, Suman K.
AU - Elias, Jack A.
PY - 2003/8
Y1 - 2003/8
N2 - 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, A 2B, and A3 but not the A2A adenosine receptors. ADA enzyme therapy diminished the IL-13-induced increase in adencsine, 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.
AB - 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, A 2B, and A3 but not the A2A adenosine receptors. ADA enzyme therapy diminished the IL-13-induced increase in adencsine, 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.
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U2 - 10.1172/JCI200316815
DO - 10.1172/JCI200316815
M3 - Article
C2 - 12897202
AN - SCOPUS:0042388120
SN - 0021-9738
VL - 112
SP - 332
EP - 344
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -