eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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1/2021
vol. 46
 
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abstract:
Experimental immunology

E2F2 stimulates CCR4 expression and activates synovial fibroblast-like cells in rheumatoid arthritis

Wanju Xu
1
,
Shufeng Li
2
,
Xiaotian Chang
1, 3

1.
Department of Clinical Laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, P.R. China
2.
Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, P.R. China
3.
Medical Research Center of the Hospital Affiliated to Qingdao University, Qingdao, Shandong, P.R. China
Cent Eur J Immunol 2021; 46 (1): 27-37
Online publish date: 2021/04/18
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Introduction
E2F transcription factor 2 (E2F2) has increased expression in synovial tissues of rheumatoid arthritis (RA) and stimulates interleukin (IL)-1 and IL- production in cultured RA synovial fibroblast-like cells (RASF), which supports the importance of E2F2 in RA pathogenesis. This study investigated the effect and mechanism of E2F2 in RA.

Material and methods
Cultured RASF were transfected with anti-E2F2 siRNA, and the expression profile was analyzed with an inflammatory response and autoimmunity PCR array loaded with 84-relative genes to explore the pathogenic pathway of E2F2. Apoptosis, migration and tube-like structure formation in the RASF with transfection of anti-E2F2 siRNA or E2F2-expressing plasmids were examined using flow cytometry, transwell assays and Matrigel assays, respectively.

Results
Significantly decreased expression of chemokine receptor 4 (CCR4) was detected in RASF with inhibited E2F2 expression, and the CCR4 expression was increased in RASF with transfection of E2F2-expressing plasmids. Silencing E2F2 expression stimulated apoptosis, but retarded migration and tube-like structure formation in RASF. The opposite observation was obtained in RASF with E2F2 overexpression.

Conclusions
High E2F2 expression decreases apoptosis and increases migration and tube-like structure ability in RASF and might perform this role by up-regulating CCR4 expression, which ultimately contributes to the disease progression of RA synovial tissues.

keywords:

CCR4, chemokine receptor 4, E2F2, E2F transcription factor 2, rheumatoid arthritis, synovial fibroblast-like cell, RASF

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