IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation
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Mast cell and basophil activation contributes to inflammation, bronchoconstriction, and airway hyperresponsiveness in asthma. Because IL-33 expression is inflammation inducible, we investigated IL-33-mediated effects in concert with both IgE-mediated and IgE-independent stimulation.
Because the HMC-1 mast cell line can be activated by GPCR and RTK signaling, we studied the effects of IL-33 on these pathways. The IL-33- and SCF-stimulated HMC-1 cells were co-cultured with human lung fibroblasts and airway smooth muscle cells in a collagen gel contraction assay. IL-33 effects on IgE-mediated activation were studied in primary mast cells and basophils.
IL-33 synergized with adenosine, C5a, SCF, and NGF receptor activation. IL-33-stimulated and SCF-stimulated HMC-1 cells demonstrated enhanced collagen gel contraction when cultured with fibroblasts or smooth muscle cells. IL-33 also synergized with IgE receptor activation of primary human mast cells and basophils.
IL-33 amplifies inflammation in both IgE-independent and IgE-dependent responses.
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- IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation
Volume 59, Issue 3 , pp 207-218
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- SP Birkhäuser Verlag Basel
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- ST2 signaling
- IgE receptor
- Adenosine receptors
- RTK signaling
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- Author Affiliations
- 1. Inflammation Research, Wyeth, 200 Cambridge Park Drive, Cambridge, MA, 02140, USA
- 2. Cell Signaling Technology, Danvers, MA, USA
- 3. Genzyme, Farmingham, MA, USA