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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-11-3396. This Article Full Text (PDF) All Versions of this Article: 2002-11-3396v1 102/1/344    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, H. Articles by Pope, R. M Search for Related Content PubMed PubMed Citation Articles by Liu, H. Articles by Pope, R. M Social Bookmarking                   What's this? Submitted November 12, 2002 Accepted February 27, 2003 Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival Hongtao Liu, Yingyu Ma, Shawn M Cole, Christopher Zander, Kun-Hung Chen, Jim Karras, and Richard M Pope* Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Division of Rheumtology, Cathay General Hospital, Taipai, Taiwan Isis Pharmaceuticals Inc., Carlsbad, CA, USA * Corresponding author; email: rmp158{at}northwestern.edu. The Bcl-2 family member Mcl-1 is essential for macrophage survival. However, the mechanisms that contribute to the expression of Mcl-1 in these cells have not been fully characterized. The present study focused on the role of STAT3 in regulation of Mcl-1 in macrophages. Sodium salicylate (NaSal) treatment induced apoptotic cell death in primary human macrophages in a dose and time-dependent fashion. Incubation with NaSal resulted in the loss of mitochondrial transmembrane potential, the release of cytochrome c and Smac/DIABLO from the mitochondria, and the activation of caspases 9 and 3. Western blot analysis and RT-PCR demonstrated that NaSal down-regulated the expression of Mcl-1. Electrophoretic mobility shift assay and Western blot analysis for phosphorylated STAT3 demonstrated that STAT3 was constitutively activated in macrophages, and that this STAT3 activation was suppressed by NaSal. The activation of STAT3 in macrophages was dependent on Ser727 phosphorylation, in the absence of detectable Tyr705 phosphorylation. Ectopic expression of STAT3 in murine RAW264.7 macrophages rescued the inhibition of Mcl-1 promoter-reporter gene activation and the cell death induced by NaSal treatment, while a dominant negative STAT3 resulted in cell death. To confirm its role in primary macrophages, STAT3 antisense (AS) oligodeoxynucleotides (ODNs) were employed. STAT3 AS, but not control, ODNs decreased STAT3 and Mcl-1 expression, and resulted in macrophage apoptosis. These observations demonstrate that the STAT3 mediated expression of Mcl-1 is essential for the survival of primary human in vitro differentiated macrophages. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Shi, T. Tran, R. Sobkoviak, and R. M. Pope Activation-induced Degradation of FLIPL Is Mediated via the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Macrophages J. Biol. Chem., May 22, 2009; 284(21): 14513 - 14523. [Abstract] [Full Text] [PDF] Q.-Q. Huang, R. Sobkoviak, A. R. Jockheck-Clark, B. Shi, A. M. Mandelin II, P. P. Tak, G. K. Haines III, C. V. Nicchitta, and R. M. Pope Heat Shock Protein 96 Is Elevated in Rheumatoid Arthritis and Activates Macrophages Primarily via TLR2 Signaling J. Immunol., April 15, 2009; 182(8): 4965 - 4973. [Abstract] [Full Text] [PDF] C. Lee, J. 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