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Int J Clin Exp Pathol 2012;5(4):299-307

Original Article
CsA improves the trophoblasts invasiveness through strengthening the cross-talk of
trophoblasts and decidual stromal cells mediated by CXCL12 and CD82 in early

Yu-Han Meng*, Jun Shao*, Hui Li, Yan-Li Hou, Chuan-Ling Tang, Mei-Rong Du, Ming-Qing Li, Da-Jin Li

Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College,
Shanghai, 200011, People’s Republic of China; Department of Pathophysiology, Soochow University Medical College, Suzhou 215123, People’
s Republic of China. *These authors contribute equally to this work.

Received March 31, 2012; accepted April 11, 2012; Epub April 16, 2012; Published May 30, 2012

Abstract: Our previous work has demonstrated that cyclosporin A (CsA) up-regulates but CD82 down-regulates the invasiveness of human
trophoblasts. In the present study, we further investigated whether CsA can modulate the trophoblasts invasion through regulating the
expression of CD82 in decidual stromal cells (DSCs). A co-culture model was established to investigate the effect of CsA on trophoblasts
invasiveness. In-cell Western was performed to evaluate the expression of CD82, p53, β-catenin and the phosphorylation level of NF-κB p50 in
DSCs. The secretion of CXCL12 of trophoblasts and DSCs was determined by enzyme-linked immunosorbent assay (ELISA). We found that
CsA could not directly change the expression of CD82 in DSCs, but the CsA-treated trophoblasts significantly enhanced CD82 expression, NF-
κB p50 phosphorylation and p53 expression, and decreased β-catenin expression in DSCs, and these effects could be abolished by anti-
CXCL12 or CXCR4 neutralizing antibody. Moreover, the invasiveness of trophoblast cells was markedly decreased after blocking CXCR4 of
trophoblasts. Interestingly, when DSCs were pretreated with anti-CXCR4 neutralizing antibody, the invasiveness of trophoblast cells was
enhanced in the co-culture unit, and blocking CXCR4 on DSCs could reverse the decrease of trophoblasts invasiveness induced by CD82.
Moreover, CsA further amplified these effects mediated by CXCL12 and CD82. Our results suggest that CsA not only promotes the trophoblasts
invasiveness through stimulating the secretion of CXCL12, but also limits the invasiveness of trophoblasts by indirectly up-regulates the
expression CD82. Therefore, CsA may contribute to the appropriate invasiveness of trophoblasts via strengthening the crosstalk between
trophoblasts and DSCs.

Keywords: CsA, CD82, trophoblasts, invasiveness, DSCs, CXCL12

Address all correspondence to:
Dr. Ming-Qing Li and Dr. Da-Jin Li
Laboratory for Reproductive Immunology
Hospital and Institute of Obstetrics and Gynecology
Fudan University Shanghai Medical College
No.413, Zhaozhou Road
Shanghai 200011, China.
Tel: 86-21-63457331; Fax: 86-21-63457331
E-mail: Dr. Ming-Qing Li <mqli1311@yahoo.com.cn>; Dr. Da-Jin Li <djli@shmu.edu.cn>