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


RESULTS
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.


CONCLUSIONS
IL-33 amplifies inflammation in both IgE-independent and IgE-dependent responses.
Silver
Matthew R
MR
Inflammation Research, Wyeth, 200 Cambridge Park Drive, Cambridge, MA, 02140, USA.
Margulis
Alexander
A
Wood
Nancy
N
Goldman
Samuel J
SJ
Kasaian
Marion
M
Chaudhary
Divya
D
D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology
D018925:Chemokines; D016207:Cytokines; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D018047:Receptors, Purinergic P1; D019089:Stem Cell Factor; D007073:Immunoglobulin E; D006632:Histamine; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4