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The Th2 Cell Cytokines IL-4 and IL-13 Regulate Found in Inflammatory Zone 1/Resistin-Like Molecule α Gene Expression by a STAT6 and CCAAT/Enhancer-Binding Protein-Dependent Mechani...
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| Zeitschriftentitel: | The Journal of Immunology |
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| Personen und Körperschaften: | , , , , , |
| In: | The Journal of Immunology, 170, 2003, 4, S. 1789-1796 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>The onset of allergic inflammation in the lung is driven by a complex genetic program. This study shows that found in inflammatory zone (FIZZ)1 and FIZZ2, but not FIZZ3, gene expression was up-regulated 6 h after Ag challenge in a mouse model of acute pulmonary inflammation. Induction of both genes was abolished in allergen-challenged STAT6-deficient mice. FIZZ1, but not FIZZ2, mRNA was up-regulated upon incubation of the myeloid cell line BMnot with IL-4. The promoter region of FIZZ1 contains functional binding sites for STAT6 and C/EBP. FIZZ1 promoter reporter gene constructs responded to IL-4 and IL-13 stimulation in transiently transfected cells. Point mutations in the STAT6 or the C/EBP site led to loss of cytokine responsiveness indicating that IL-4-mediated induction of murine FIZZ1 is orchestrated by the coordinate action of STAT6 and C/EBP. It is concluded that the expression of the genes encoding FIZZ1 and FIZZ2, but not FIZZ3, is induced in allergen-challenged lungs in a STAT6-dependent fashion. STAT6 directly regulates IL-4- and IL-13-triggered induction of FIZZ1 expression at the transcriptional level by cooperation with C/EBP. Induction of FIZZ2 gene expression most likely occurs independent of a direct effect by these cytokines and may be due to indirect STAT6-driven mechanisms.</jats:p> |
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| Umfang: | 1789-1796 |
| ISSN: |
0022-1767
1550-6606 |
| DOI: | 10.4049/jimmunol.170.4.1789 |