An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion

Hiroya Miyamoto, Eri Katsuyama, Yoshiteru Miyauchi, Hiroko Hoshi, Kana Miyamoto, Yuiko Sato, Tami Kobayashi, Ryotaro Iwasaki, Shigeyuki Yoshida, Tomoaki Mori, Hiroya Kanagawa, Atsuhiro Fujie, Wu Hao, Hideo Morioka, Morio Matsumoto, Yoshiaki Toyama, Takeshi Miyamoto

研究成果: Article査読

28 被引用数 (Scopus)

抄録

Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs) form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we reported that two seven-transmembrane molecules, osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in vivo and in vitro. However, signaling required to regulate FBGC fusion remained largely unknown. Here, we show that signal transducer and activator of transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1 activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co-expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and DC-STAMP expression and governs fusogenic mechanisms in FBGCs.

本文言語English
ページ(範囲)32479-32484
ページ数6
ジャーナルJournal of Biological Chemistry
287
39
DOI
出版ステータスPublished - 2012 9 21

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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