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IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation

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Abstract

Objective

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.

Methods

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.

Result

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.

Conclusion

IL-33 amplifies inflammation in both IgE-independent and IgE-dependent responses.

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Acknowledgments

We thank Dr. Karl Nocka for advice and expertise in the generation of primary human mast cells.

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Correspondence to Divya Chaudhary.

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Responsible Editor: A. Falus.

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Silver, M.R., Margulis, A., Wood, N. et al. IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation. Inflamm. Res. 59, 207–218 (2010). https://doi.org/10.1007/s00011-009-0088-5

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