Inflammation Research

, Volume 59, Issue 3, pp 207–218 | Cite as

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

  • Matthew R. Silver
  • Alexander Margulis
  • Nancy Wood
  • Samuel J. Goldman
  • Marion Kasaian
  • Divya Chaudhary
Original Research Paper

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.

Keywords

ST2 signaling HMC-1 IgE receptor Adenosine receptors RTK signaling 

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Matthew R. Silver
    • 1
    • 2
  • Alexander Margulis
    • 1
    • 3
  • Nancy Wood
    • 1
  • Samuel J. Goldman
    • 1
  • Marion Kasaian
    • 1
  • Divya Chaudhary
    • 1
  1. 1.Inflammation ResearchWyethCambridgeUSA
  2. 2.Cell Signaling TechnologyDanversUSA
  3. 3.GenzymeFarminghamUSA

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