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Adenosine metabolism and murine strain-specific IL-4-induced inflammation, emphysema, and fibrosis

Ma, Bing ; Blackburn, Michael R ; Lee, Chun Geun ; Homer, Robert J ; Liu, Wei ; Flavell, Richard A ; Boyden, Lynn ; Lifton, Richard P ; Sun, Chun-Xiao ; Young, Hays W ; Elias, Jack A

The Journal of clinical investigation, 2006-05, Vol.116 (5), p.1274-1283 [Periódico revisado por pares]

United States: American Society for Clinical Investigation

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Título:
Adenosine metabolism and murine strain-specific IL-4-induced inflammation, emphysema, and fibrosis
Autor: Ma, Bing ; Blackburn, Michael R ; Lee, Chun Geun ; Homer, Robert J ; Liu, Wei ; Flavell, Richard A ; Boyden, Lynn ; Lifton, Richard P ; Sun, Chun-Xiao ; Young, Hays W ; Elias, Jack A
Assuntos: Adenosine ; Adenosine - metabolism ; Animals ; Biomedical research ; Chronic obstructive pulmonary disease ; Cytokines ; Emphysema - pathology ; Female ; Fibrosis - pathology ; Genetic research ; Inflammation ; Interleukin-4 - metabolism ; Interleukin-4 - physiology ; Lavage ; Male ; Medical research ; Medicine, Experimental ; Metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Polyethylene glycol ; Pulmonary Alveoli - metabolism ; Rats ; Species Specificity ; Transforming Growth Factor beta - metabolism ; Transforming Growth Factor beta1
É parte de: The Journal of clinical investigation, 2006-05, Vol.116 (5), p.1274-1283
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: To define the factors that control the tissue effects of IL-4, we compared the effects of Tg IL-4 in Balb/c and C57BL/6 mice. In the former, IL-4 caused modest eosinophilic inflammation and mild airway fibrosis and did not shorten survival. In C57BL/6 mice, IL-4 caused profound eosinophilic inflammation, airway fibrosis, emphysematous alveolar destruction, and premature death. These differences could not be accounted for by changes in Th2 or Th1 cytokines, receptor components, STAT6 activation, MMPs, or cathepsins. In contrast, in C57BL/6 mice, alveolar remodeling was associated with decreased levels of tissue inhibitors of metalloproteinase 2, -3, and -4 and alpha1-antitrypsin, and fibrosis was associated with increased levels of total and bioactive TGF-beta1. Impressive differences in adenosine metabolism were also appreciated, with increased tissue adenosine levels and A(1), A(2B), and A(3) adenosine receptor expression and decreased adenosine deaminase (ADA) activity in C57BL/6 animals. Treatment with ADA also reduced the inflammation, fibrosis, and emphysematous destruction and improved the survival of C57BL/6 Tg animals. These studies demonstrate that genetic influences control IL-4 effector pathways in the murine lung. They also demonstrate that IL-4 has different effects on adenosine metabolism in Balb/c and C57BL/6 mice and that these differences contribute to the different responses that IL-4 induces in these inbred animals.
Editor: United States: American Society for Clinical Investigation
Idioma: Inglês

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Adenosine metabolism and murine strain-specific IL-4-induced inflammation, emphysema, and fibrosis

Ma, Bing ; Blackburn, Michael R ; Lee, Chun Geun ; Homer, Robert J ; Liu, Wei ; Flavell, Richard A ; Boyden, Lynn ; Lifton, Richard P ; Sun, Chun-Xiao ; Young, Hays W ; Elias, Jack A

United States: American Society for Clinical Investigation

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