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Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33: implications for allergic inflammation

Cellular & Molecular Immunology volume 7, pages 26–34 (2010)Cite this article

Abstract

The novel interleukin (IL)-1 family cytokine IL-33 has been shown to activate T helper 2 (Th2) lymphocytes, mast cells and basophils to produce an array of proinflammatory cytokines, as well as to mediate blood eosinophilia, IgE secretion and hypertrophy of airway epithelium in mice. In the present study, we characterized the activation of human eosinophils by IL-33, and investigated the underlying intracellular signaling mechanisms. IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule (ICAM)-1 on eosinophils, but it suppressed that of ICAM-3 and L-selectin. In addition, IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2. We found that IL-33-mediated enhancement of survival, induction of adhesion molecules, and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we compared the above IL-33 activities with two structurally and functionally related cytokines, IL-1β and IL-18. IL-1β, but not IL-18, markedly upregulated cell surface expression of ICAM-1. IL-1β and IL-18 also significantly enhanced eosinophil survival, and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB, p38 MAPK and ERK pathways. Synergistic effects on the release of IL-6 were also observed in combined treatment with IL-1β, IL-18 and IL-33. Taken together, our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.

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Acknowledgements

This study was supported by Research Grant Committee General Research Fund, Hong Kong (Project code: CU08757; principal investigator: CK Wong; co-investigator: CWK Lam).

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  1. Joyce YS Chow and Chun K Wong: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China

    Joyce YS Chow, Chun K Wong, Phyllis FY Cheung & Christopher WK Lam

  2. Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology Foundation, Macau, China

    Christopher WK Lam

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  1. Joyce YS Chow
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Correspondence to Chun K Wong.

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Chow, J., Wong, C., Cheung, P. et al. Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33: implications for allergic inflammation. Cell Mol Immunol 7, 26–34 (2010). https://doi.org/10.1038/cmi.2009.106

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