Eosinophilic differentiation is promoted by blockage of Notch signaling with a gamma-secretase inhibitor

Jin Hyun Kang, Da Hye Lee, Jong Soo Lee, Hai Joong Kim, Jin Woo Shin, Young Han Lee, Young Seek Lee, Choon Sik Park, Il Yup Chung

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22 Citations (Scopus)

Abstract

Although increasing evidence supports the inhibitory role of Notch in granulocyte differentiation, the direct effects of Notch on the differentiation and maturation of eosinophils, one type of granulocyte, have not yet been studied. We investigated whether a blockage of Notch signaling promoted the differentiation of eosinophils from umbilical cord blood (UCB) cells. Freshly isolated UCB cells were cultured with IL-3, IL-5 and GM-CSF in the presence or absence of a γ-secretase inhibitor L-685,458, and examined for the expression of major basic protein (MBP). Freshly isolated UCB cells expressed mRNA and proteins for Notch 1, Notch 2, Delta 1, and Jagged 1. MBP expression in cultures with the inhibitor was significantly increased, as compared with the cultures in the absence of the inhibitor. Treatment with the inhibitor was accompanied by a decrease in Hes 1 mRNA expression, indicative of Notch-mediated signaling for the inhibitor effect. UCB cells cultured with the inhibitor for 28 days displayed similar levels of CCR3, a late marker of eosinophil development, as compared with the cells cultured without the inhibitor, but almost completely lost chemotaxis response to eotaxin. Our data suggest that Notch signaling may modulate eosinophil migration at the mature stage as well as inhibit eosinophil differentiation.

Original languageEnglish
Pages (from-to)2982-2990
Number of pages9
JournalEuropean Journal of Immunology
Volume35
Issue number10
DOIs
Publication statusPublished - 2005 Oct

Keywords

  • CCR3
  • Cord blood
  • Eosinophil
  • Gamma-secretase inhibitor
  • Notch

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kang, J. H., Lee, D. H., Lee, J. S., Kim, H. J., Shin, J. W., Lee, Y. H., Lee, Y. S., Park, C. S., & Chung, I. Y. (2005). Eosinophilic differentiation is promoted by blockage of Notch signaling with a gamma-secretase inhibitor. European Journal of Immunology, 35(10), 2982-2990. https://doi.org/10.1002/eji.200526242