Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis
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 sy...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/350209 |
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| author | Zhijun Jiao Wenhong Wang Jie Ma Shengjun Wang Zhaoliang Su Huaxi Xu |
| author_facet | Zhijun Jiao Wenhong Wang Jie Ma Shengjun Wang Zhaoliang Su Huaxi Xu |
| author_sort | Zhijun Jiao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-532c3de29d1e4fc09e37779543ba507c |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Clinical and Developmental Immunology |
| spelling | doaj-art-532c3de29d1e4fc09e37779543ba507c2025-02-03T05:58:25ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/350209350209Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid ArthritisZhijun Jiao0Wenhong Wang1Jie Ma2Shengjun Wang3Zhaoliang Su4Huaxi Xu5Key Laboratory of Medical Immunology and Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, ChinaDepartment of Pathogenic Biology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, ChinaDepartment of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, ChinaIt 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.http://dx.doi.org/10.1155/2012/350209 |
| spellingShingle | Zhijun Jiao Wenhong Wang Jie Ma Shengjun Wang Zhaoliang Su Huaxi Xu Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis Clinical and Developmental Immunology |
| title | Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis |
| title_full | Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis |
| title_fullStr | Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis |
| title_full_unstemmed | Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis |
| title_short | Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis |
| title_sort | notch signaling mediates tnf α induced il 6 production in cultured fibroblast like synoviocytes from rheumatoid arthritis |
| url | http://dx.doi.org/10.1155/2012/350209 |
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