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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 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 (US)
Pages (from-to)8337-8345
Number of pages9
JournalJournal of Immunology
Volume175
Issue number12
DOIs
StatePublished - Dec 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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