Mcl-1 is essential for the survival of synovial fibroblasts in rheumatoid arthritis

Hongtao Liu, Polikseni Eksarko, Vladislav Temkin, G. Kenneth Haines, Harris Perlman, Alisa E. Koch, Bayar Thimmapaya, Richard M. Pope

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

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-α, and IL-1β 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.

Original languageEnglish
Pages (from-to)8337-8345
Number of pages9
JournalJournal of Immunology
Volume175
Issue number12
DOIs
StatePublished - 15 Dec 2005
Externally publishedYes

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