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A more recent version of this article appeared on November 1, 2007

Published online before print July 26, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1106697

Received for publication November 26, 2006.
Revised June 12, 2007.
Accepted for publication June 18, 2007.

Article

Chemokine stromal cell-derived factor-1 induction by C/EBP{beta} activation is associated with all-trans-retinoic acid-induced leukemic cell differentiation

KyeongJin Kim *, Hyeong Hoe Kim {dagger}, Joon Hong Kim {dagger}, Yung Hyun Choi {ddagger}, Young Hee Kim *, and JaeHun Cheong *@

Departments of *Molecular Biology, College of Natural Sciences, and {dagger}Laboratory Medicine, College of Medical Sciences, Pusan National University, Busan, Korea; and {ddagger}Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Korea

@ To whom correspondence should be addressed. E-mail: molecule85{at}pusan.ac.kr.


  Abstract

Stromal cell-derived factor-1 (SDF-1/CXCL12) is one of the essential chemokines, which mediates hematopoietic differentiations. However, the mechanism by which SDF-1 expression is regulated in granulocyte differentiation is poorly understood. Here, we suggest a novel mechanism by which all-trans-retinoic acid (ATRA) induces the expression of SDF-1 during the differentiation of promyelomonocytic leukemic U937 cells. Moreover, we also demonstrate that activation of transcription factor C/EBP{beta} by ATRA regulates SDF-1 expression in U937 cells. In addition, we show that the cyclin-dependent kinase inhibitors p21WAF1/CIP1 and Pyk2 are up-regulated by SDF-1 and increased markedly by the costimulation of ATRA and SDF-1. Furthermore, ATRA and SDF-1{alpha} additively induce U937 cell differentiation. Indeed, silencing the expression of SDF-1 inhibits ATRA-induced granulocyte differentiation significantly. Taken together, these results indicate that SDF-1{alpha} is involved in granulocyte differentiation in response to ATRA, mediated by the activation of the transcription factor C/EBP{beta}.

Key Words: SDF-1 • granulocyte






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