STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-κB p65

T. Kawashima, K. Murata, S. Akira, Y. Tonozuka, Y. Minoshima, S. Feng, H. Kumagai, H. Tsuruga, Y. Ikeda, S. Asano, T. Nosaka, T. Kitamura

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37 Scopus citations

Abstract

We recently demonstrated that STAT5 can induce a variety of biological functions in mouse IL-3-dependent Ba/F3 cells; STAT5-induced expression of pim-1, p21WAF/Cip1, and suppressor of cytokine signaling-1/STAT-induced STAT inhibitor-1/Janus kinase binding protein is responsible for induction of proliferation, differentiation, and apoptosis, respectively. In the present study, using a constitutively active STAT5A (STAT5A1*6), we show that STAT5 induces macrophage differentiation of mouse leukemic M1 cells through a distinct mechanism, autocrine production of IL-6. The supernatant of STAT5A1*6-transduced cells contained sufficient concentrations of IL-6 to induce macrophage differentiation of parental M1 cells, and STAT3 was phosphorylated on their tyrosine residues in these cells. Treatment of the cells with anti-IL-6 blocking Abs profoundly inhibited the differentiation. We also found that the STAT5A1*6 transactivated the IL-6 promoter, which was mediated by the enhanced binding of NF-κB p65 (RelA) to the promoter region of IL-6. These findings indicate that STAT5A cooperates with Rel/NF-κB to induce production of IL-6, thereby inducing macrophage differentiation of M1 cells in an autocrine manner. In summary, we have shown a novel mechanism by which STAT5 induces its pleiotropic functions.

Original languageEnglish (US)
Pages (from-to)3652-3660
Number of pages9
JournalJournal of Immunology
Volume167
Issue number7
StatePublished - Oct 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kawashima, T., Murata, K., Akira, S., Tonozuka, Y., Minoshima, Y., Feng, S., Kumagai, H., Tsuruga, H., Ikeda, Y., Asano, S., Nosaka, T., & Kitamura, T. (2001). STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-κB p65. Journal of Immunology, 167(7), 3652-3660.