Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.
J Allergy Clin Immunol
; 123(4): 795-804.e8, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19249085
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Interleucina-4
/
Interleucina-13
/
Perfilação da Expressão Gênica
/
Pulmão
Limite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos