In:
The Journal of Immunology, The American Association of Immunologists, Vol. 174, No. 8 ( 2005-04-15), p. 4630-4638
Abstract:
Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, and only the latter is also activated by IL-13, IL-13 contributes more than IL-4 to goblet cell hyperplasia and airway hyperresponsiveness in murine asthma. To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR. Only the collagen α2 type VI (Ca2T6) gene and three small proline-rich protein (SPRR) genes were reproducibly induced & gt;4-fold more by IL-13 than by IL-4. Preferential IL-13 gene induction was not attributable to B cells, T cells, or differences in cytokine potency. IL-4 signaling through IL-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ production does not suppress the Ca2T6 or SPRR genes. Thus, IL-4 induces genes in addition to IL-12 that suppress STAT6-mediated SPRR gene induction. These results provide a potential explanation for the dominant role of IL-13 in induction of goblet cell hyperplasia and airway hyperresponsiveness in asthma.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.174.8.4630
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2005
detail.hit.zdb_id:
1475085-5
detail.hit.zdb_id:
3056-9
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