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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 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 Citation Map 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. Related Collections Apoptosis Signal Transduction Gene Expression Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 344-352 PHAGOCYTES 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 From the Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Cathay General Hospital, Taipei, Taiwan; and Isis Pharmaceuticals Inc, Carlsbad, CA. 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 signal transducer and activator of transcription 3 (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 cytochromecand second mitochondria-derived activator of caspase/direct IAP binding protein with low pH of isoelectric point (pI) from the mitochondria, and the activation of caspases 9 and 3. Western blot analysis and reverse transcription—polymerase chain reaction 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 Tyr705phosphorylation. 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. (Blood. 2003;102:344-352) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Duplomb, M. Baud'huin, C. Charrier, M. Berreur, V. Trichet, F. Blanchard, and D. 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