Mcl-1 is essential for the survival of synovial fibroblasts in rheumatoid arthritis
Mcl-1 is essential for the survival of synovial fibroblasts in rheumatoid arthritis
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DOI：
10.4049/jimmunol.175.12.8337
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发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Pope, RM
中科院分区：
文献类型：
--
作者：
Liu, HT;Eksarko, P;Pope, RM
Mcl-1 is a Bcl-2-family, antiapoptotic molecule that is critical for the survival of T and B lymphocytes and macrophages; however, its role in nonhemopoietic cells remains to be fully elucidated. The current study focuses on the role of Mcl-1 in rheumatoid arthritis (RA). Mcl-1 was strongly expressed in the synovial lining and was increased in the sublining fibroblasts of patients with RA, compared with control synovial tissue. The expression of Mcl-1 in sublining fibroblasts correlated with the degree of inflammation and TNF-alpha, and IL-1 beta treatment of cultured synovial fibroblasts resulted in the increased expression of Mcl-1 at the mRNA and protein levels. Mcl-1 was critical for the survival of RA synovial fibroblasts, because the forced reduction of Mcl-1 using a Mcl-1 antisense-expressing adenoviral vector induced apoptotic cell death, which was mediated through Bax, Bak, and Bim. These observations document a critical role for Mcl-1 in protecting against apoptosis in RA and suggest that Mcl-1 is a potential therapeutic target in this disease.
