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Published online before print July 26, 2007

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(Journal of Leukocyte Biology. 2007;82:1332-1339.)
© 2007 by Society for Leukocyte Biology

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

KyeongJin Kim^*, Hyeong Hoe Kim, Joon Hong Kim, Yung Hyun Choi, Young Hee Kim^*,1 and JaeHun Cheong^*,1

^* Departments of Molecular Biology, College of Natural Sciences, Pusan National University, Korea; Departments of
Laboratory Medicine and
Internal Medicine, College of Medical Sciences, Pusan National University, Busan Korea; and
Department of Biochemistry, College of Oriental Medicine, Dongeui University, Buscan, Korea

¹ Correspondence: Department of Molecular Biology, Pusan National University, Busan, 609-735, Korea. E-mail: molecule85{at}pusan.ac.kr

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/EBPβ by ATRA regulates SDF-1 expression in U937 cells. In addition, we show that the cyclin-dependent kinase inhibitors p21^WAF1/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 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 is involved in granulocyte differentiation in response to ATRA, mediated by the activation of the transcription factor C/EBPβ.

Key Words: SDF-1 • granulocyte • ATRA • p21