title: Interleukin-6 contributes to inflammation and remodeling in a model of adenosine mediated lung injury.
abstract: BACKGROUND
  Chronic lung diseases are the third leading cause of death in the United States due in part to an incomplete understanding of pathways that govern the progressive tissue remodeling that occurs in these disorders. Adenosine is elevated in the lungs of animal models and humans with chronic lung disease where it promotes air-space destruction and fibrosis. Adenosine signaling increases the production of the pro-fibrotic cytokine interleukin-6 (IL-6). Based on these observations, we hypothesized that IL-6 signaling contributes to tissue destruction and remodeling in a model of chronic lung disease where adenosine levels are elevated.
  
  
  RESULTS
  We tested this hypothesis by neutralizing or genetically removing IL-6 in adenosine deaminase (ADA)-deficient mice that develop adenosine dependent pulmonary inflammation and remodeling. Results demonstrated that both pharmacologic blockade and genetic removal of IL-6 attenuated pulmonary inflammation, remodeling and fibrosis in this model. The pursuit of mechanisms involved revealed adenosine and IL-6 dependent activation of STAT-3 in airway epithelial cells.
  
  
  CONCLUSIONS
  These findings demonstrate that adenosine enhances IL-6 signaling pathways to promote aspects of chronic lung disease. This suggests that blocking IL-6 signaling during chronic stages of disease may provide benefit in halting remodeling processes such as fibrosis and air-space destruction.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Texas, United States of America.
authors.forename: Mesias
authors.initials: M
authors.lastname: Pedroza
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schneider
authors.forename: Harry
authors.initials: H
authors.lastname: Karmouty-Quintana
authors.forename: Julie
authors.initials: J
authors.lastname: Coote
authors.forename: Stevan
authors.initials: S
authors.lastname: Shaw
authors.forename: Rebecca
authors.initials: R
authors.lastname: Corrigan
authors.forename: Jose G
authors.initials: JG
authors.lastname: Molina
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Alcorn
authors.forename: David
authors.initials: D
authors.lastname: Galas
authors.forename: Richard
authors.initials: R
authors.lastname: Gelinas
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blackburn
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055370:Lung Injury / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000150:complications / Q000188:drug therapy; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000243:Adenosine Deaminase; D000241:Adenosine