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PMID:17623648
| Citation |
Hayakawa, H, Hayakawa, M, Kume, A and Tominaga, S (2007) Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J. Biol. Chem. 282:26369-80 |
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| Abstract |
The ST2 gene produces a soluble secreted form and a transmembrane form, referred to as soluble ST2 and ST2L, respectively. A recent study has reported that interleukin (IL)-33 is a specific ligand of ST2L and induces production of T helper type 2 (Th2) cytokines. Although soluble ST2 is highly produced in sera of asthmatic patients and plays a critical role for production of Th2 cytokines, the function of soluble ST2 in relation to IL-33 signaling remains unclear. Here we show antagonistic effects of soluble ST2 on IL-33 signaling using a murine thymoma EL-4 cells stably expressing ST2L and a murine model of asthma. Soluble ST2 directly bound to IL-33 and suppressed activation of NF-kappaB in EL-4 cells stably expressing ST2L, suggesting that the complex of soluble ST2 and IL-33 fails to bind to ST2L. In a murine model of asthma, pretreatment with soluble ST2 reduced production of IL-4, IL-5, and IL-13 from IL-33-stimulated splenocytes. These results indicate that soluble ST2 acts as a negative regulator of Th2 cytokine production by the IL-33 signaling. Our study provides a molecular mechanism wherein soluble ST2 modulates the biological activity of IL-33 in allergic airway inflammation. |
| Links |
PubMed Online version:10.1074/jbc.M704916200 |
| Keywords |
Animals; Asthma/immunology; Asthma/pathology; Cell Line, Tumor; Cytokines/immunology; Disease Models, Animal; Humans; Interleukins/immunology; Interleukins/pharmacology; Male; Membrane Proteins/immunology; Membrane Proteins/pharmacology; Mice; Mice, Inbred BALB C; NF-kappa B/immunology; Receptors, Cell Surface/immunology; Receptors, Interleukin; Signal Transduction/drug effects; Signal Transduction/immunology; Th2 Cells/immunology; Th2 Cells/pathology |
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Significance
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| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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