If the speed of the IL-4/13-Trap is the same as for VEGF-T, maybe somewhere in 2XXX wemay get clue what is going on?
J. Clin. Invest. 112:332-344 (2003). doi:10.1172/JCI200316815.
Copyright ©2003 by the American Society for Clinical Investigation
Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathway
Michael R. Blackburn1, Chun G. Lee2, Hays W.J. Young1, Zhou Zhu2, Janci L. Chunn1, Min Jong Kang2, Suman K. Banerjee1 and Jack A. Elias2
1Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas, USA
2Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
Address correspondence to: Jack A. Elias, Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, S441-C, New Haven, Connecticut 06520-8057, USA. Phone: (203) 785-4163; Fax: (203) 785-3826; E-mail: jack.elias@yale.edu.
Received for publication September 3, 2002, and accepted in revised form May 6, 2003.
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. |
