title: Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.
abstract: BACKGROUND
  Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive.
  
  
  OBJECTIVE
  We sought to clarify the role or roles of IL-4 and IL-13 in asthma-pathogenesis.
  
  
  METHODS
  We used DNA Affymetrix microarrays to profile pulmonary gene expression in BALB/c mice inoculated intratracheally with ragweed pollen, house dust mite, IL-4, IL-13, or both cytokines. IL-13 dependence was confirmed by comparing pulmonary gene expression in house dust mite-inoculated wild-type and IL-13 knockout mice.
  
  
  RESULTS
  A signature gene expression profile consisting of 23 genes was commonly induced by means of inoculation with house dust mite, ragweed pollen, or IL-4 plus IL-13. Although rIL-4 and rIL-13 treatment induced an overlapping set of genes, IL-4 uniquely induced 21 genes, half of which were interferon response genes and half of which were genes important in immunoregulation. IL-13 uniquely induced 8 genes, most of which encode proteins produced by epithelial cells.
  
  
  CONCLUSIONS
  IL-4 and IL-13 together account for most allergen-induced pulmonary genes. Selective IL-4 induction of IFN-gamma response genes and other genes that might negatively regulate allergic inflammation could partially explain the greater importance of IL-13 in the effector phase of allergic airway disease.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Lewis
authors.forename: Bruce
authors.initials: B
authors.lastname: Aronow
authors.forename: John
authors.initials: J
authors.lastname: Hutton
authors.forename: Joanna
authors.initials: J
authors.lastname: Santeliz
authors.forename: Krista
authors.initials: K
authors.lastname: Dienger
authors.forename: Nancy
authors.initials: N
authors.lastname: Herman
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology*; D005260:Female; D020869:Gene Expression Profiling; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019948:Receptors, Interleukin-4 / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000485:Allergens; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4