TY - JOUR
T1 - A novel IL-1 family cytokine, IL-33, potently activates human eosinophils
AU - Cherry, W. Brett
AU - Yoon, Juhan
AU - Bartemes, Kathleen R.
AU - Iijima, Koji
AU - Kita, Hirohito
N1 - Funding Information:
Supported by National Institutes of Health grant R01AI34486 and the Mayo Foundation.
PY - 2008/6
Y1 - 2008/6
N2 - Background: Eosinophils are likely key cells involved in the pathogenesis of asthma and allergic diseases; however, the mechanisms that regulate eosinophil dynamics and functions in mucosal tissues are incompletely understood. IL-33, which is produced by mucosal cells, is a new member of the IL-1 cytokine family. Mice injected with IL-33 display profound mucosal eosinophilia with associated pathologic changes. Although mast cells and TH2 cells express the IL-33 receptor, ST2, the roles of IL-33 and ST2 in eosinophil biology are unknown. Objectives: We investigated the effects of IL-33 on human eosinophils in vitro. Methods: Eosinophils and neutrophils were isolated from blood of normal individuals and mildly atopic patients. Real-time RT-PCR and flow cytometry were used to detect ST2. Granulocyte responses to IL-33 were monitored by superoxide anion production and by degranulation; IL-5, IL-1β, and TNF-α served as controls. Eosinophil survival and cytokine production were assessed by flow cytometry and ELISA, respectively. Results: ST2 mRNA and protein were detected on eosinophils. IL-33 induced eosinophil superoxide anion production and degranulation as potently as IL-5. IL-33 also increased eosinophil survival and induced production of IL-8. Anti-ST2 inhibited eosinophil responses to IL-33. Neutrophils did not express ST2, nor did they respond to IL-33. Conclusion: IL-33 and its receptor, ST2, may play important roles in eosinophil-mediated inflammation; they may provide new therapeutic targets for controlling mucosal eosinophilic inflammation.
AB - Background: Eosinophils are likely key cells involved in the pathogenesis of asthma and allergic diseases; however, the mechanisms that regulate eosinophil dynamics and functions in mucosal tissues are incompletely understood. IL-33, which is produced by mucosal cells, is a new member of the IL-1 cytokine family. Mice injected with IL-33 display profound mucosal eosinophilia with associated pathologic changes. Although mast cells and TH2 cells express the IL-33 receptor, ST2, the roles of IL-33 and ST2 in eosinophil biology are unknown. Objectives: We investigated the effects of IL-33 on human eosinophils in vitro. Methods: Eosinophils and neutrophils were isolated from blood of normal individuals and mildly atopic patients. Real-time RT-PCR and flow cytometry were used to detect ST2. Granulocyte responses to IL-33 were monitored by superoxide anion production and by degranulation; IL-5, IL-1β, and TNF-α served as controls. Eosinophil survival and cytokine production were assessed by flow cytometry and ELISA, respectively. Results: ST2 mRNA and protein were detected on eosinophils. IL-33 induced eosinophil superoxide anion production and degranulation as potently as IL-5. IL-33 also increased eosinophil survival and induced production of IL-8. Anti-ST2 inhibited eosinophil responses to IL-33. Neutrophils did not express ST2, nor did they respond to IL-33. Conclusion: IL-33 and its receptor, ST2, may play important roles in eosinophil-mediated inflammation; they may provide new therapeutic targets for controlling mucosal eosinophilic inflammation.
KW - Eosinophils
KW - IL-33
KW - ST2
KW - activation
KW - inflammation
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U2 - 10.1016/j.jaci.2008.04.005
DO - 10.1016/j.jaci.2008.04.005
M3 - Article
C2 - 18539196
AN - SCOPUS:44649129170
SN - 0091-6749
VL - 121
SP - 1484
EP - 1490
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -