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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 350209, 6 pages
Research Article

Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis

1Key Laboratory of Medical Immunology and Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, China
2Department of Pathogenic Biology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China
3Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China

Received 25 June 2011; Revised 6 September 2011; Accepted 23 September 2011

Academic Editor: Britt Nakken

Copyright © 2012 Zhijun Jiao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


It has been reported that Notch family proteins are expressed in synovium tissue and involved in the proliferation of synoviocyte from rheumatoid arthritis (RA). The aim of this paper was to investigate whether Notch signaling mediated TNF-α-induced cytokine production of cultured fibroblast-like synoviocytes (FLSs) from RA. Exposure of RA FLSs to TNF-α (10 ng/ml) led to increase of Hes-1, a target gene of Notch signaling, and a marked upregulation of Notch 2, Delta-like 1, and Delta-like 3 mRNA levels. Blockage of Notch signaling by a γ-secretase inhibitor (DAPT) inhibited IL-6 secretion of RA FLSs in response to TNF-α while treatment with recombinant fusion protein of Notch ligand Delta-like 1 promoted such response. TNF-α stimulation also induced IL-6 secretion in OA FLSs; however, the Hes-1 level remained unaffected. Our data confirm the functional involvement of Notch pathway in the pathophysiology of RA FLSs which may provide a new target for RA therapy.