BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production

Raymond Yick Loi Yu, Xing Wang, Fiona J. Pixley, J. Jessica Yu, Alexander L. Dent, Hal E. Broxmeyer, E. Richard Stanley, B. Hilda Ye

Research output: Contribution to journalArticle

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Abstract

The transcription repressor BCL-6 is known to play critical roles in B-cell lymphomagenesis, germinal center formation, and balanced Th1/Th2 differentiation. In macrophages, although BCL-6 has also been shown to regulate the expression of several chemokine genes, its function in other aspects of macrophage biology has not been studied. In addition, the precise role of BCL-6 in cell proliferation is poorly understood in general. Here we report that BCL-6-/- macrophages hyperproliferate due to an accelerated G 1/S transition accompanied by increased cyclin D2 and c-myc and decreased expression of p27. Crucial to this enhanced proliferation is spontaneous interleukin 6 (IL-6) production and signal transducer and activator of transcription 3 (STAT3) activation in BCL-6-/- macrophages. In colony-forming assays, BCL-6-/- bone marrow progenitor cells form spontaneous macrophage colonies that can be inhibited by anti-IL-6 antibodies. Gene expression studies demonstrate that BCL-6 binds to several sequence motifs scattered in the IL-6 locus and can repress IL-6 transcription both in 293T cells and in macrophages. In conclusion, our results indicate that BCL-6 negatively regulates proliferation of the monocytic/macrophage lineage by suppressing an autocrine IL-6/STAT3-mediated gene expression program. Our work also suggests that BCL-6 prevents abnormal Th2 differentiation by suppressing basal level IL-6 production in antigen-presenting cells (APCs).

Original languageEnglish (US)
Pages (from-to)1777-1784
Number of pages8
JournalBlood
Volume105
Issue number4
DOIs
StatePublished - Feb 15 2005

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Macrophages
Interleukin-6
STAT3 Transcription Factor
Transcription
Gene expression
Cyclin D2
Gene Expression
Germinal Center
HEK293 Cells
Cell proliferation
Antigen-Presenting Cells
Chemokines
Bone Marrow Cells
Transcriptional Activation
Assays
Bone
B-Lymphocytes
Stem Cells
Genes
Chemical activation

ASJC Scopus subject areas

  • Hematology

Cite this

Yu, R. Y. L., Wang, X., Pixley, F. J., Yu, J. J., Dent, A. L., Broxmeyer, H. E., ... Ye, B. H. (2005). BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. Blood, 105(4), 1777-1784. https://doi.org/10.1182/blood-2004-08-3171

BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. / Yu, Raymond Yick Loi; Wang, Xing; Pixley, Fiona J.; Yu, J. Jessica; Dent, Alexander L.; Broxmeyer, Hal E.; Stanley, E. Richard; Ye, B. Hilda.

In: Blood, Vol. 105, No. 4, 15.02.2005, p. 1777-1784.

Research output: Contribution to journalArticle

Yu, RYL, Wang, X, Pixley, FJ, Yu, JJ, Dent, AL, Broxmeyer, HE, Stanley, ER & Ye, BH 2005, 'BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production', Blood, vol. 105, no. 4, pp. 1777-1784. https://doi.org/10.1182/blood-2004-08-3171
Yu RYL, Wang X, Pixley FJ, Yu JJ, Dent AL, Broxmeyer HE et al. BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. Blood. 2005 Feb 15;105(4):1777-1784. https://doi.org/10.1182/blood-2004-08-3171
Yu, Raymond Yick Loi ; Wang, Xing ; Pixley, Fiona J. ; Yu, J. Jessica ; Dent, Alexander L. ; Broxmeyer, Hal E. ; Stanley, E. Richard ; Ye, B. Hilda. / BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. In: Blood. 2005 ; Vol. 105, No. 4. pp. 1777-1784.
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