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

Title
Eosinophilic differentiation is promoted by blockage of Notch signaling with a gamma-secretase inhibitor
Author
이영식
Keywords
CCR3; cord blood; eosinophil; Notch; gamma-secretase inhibitor
Issue Date
2005-10
Publisher
WILEY-V C H VERLAG GMBH
Citation
EUROPEAN JOURNAL OF IMMUNOLOGY, v. 35, No. 10, Page. 2982-2990
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 gamma-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.
URI
https://onlinelibrary.wiley.com/doi/full/10.1002/eji.200526242http://repository.hanyang.ac.kr/handle/20.500.11754/111671
ISSN
0014-2980; 1521-4141
DOI
10.1002/eji.200526242
Appears in Collections:
COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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