The Golgi-associated protein p115 mediates the secretion of macrophage migration inhibitory factor.

نویسندگان

  • Melanie Merk
  • John Baugh
  • Swen Zierow
  • Lin Leng
  • Utpal Pal
  • Seung Joon Lee
  • Antje D Ebert
  • Yuka Mizue
  • John O Trent
  • Robert Mitchell
  • Walter Nickel
  • Paula B Kavathas
  • Jürgen Bernhagen
  • Richard Bucala
چکیده

Macrophage migration inhibitory factor (MIF) is a leaderless protein that is secreted from cells by a specialized, nonclassical export pathway. The release of MIF nevertheless is regulated and its production in response to different inflammatory, mitogenic, and hormonal stimuli plays an important role in diverse physiologic and pathologic processes. We report herein the identification of the Golgi complex-associated protein p115 as an intracellular binding partner for MIF. MIF interacts with p115 in the cytoplasm and the stimulated secretion of MIF results in the accumulation of both proteins in supernatants, which is consistent with MIF release from cells in conjunction with p115. The depletion of p115 from monocytes/macrophages decreases the release of MIF but not other cytokines following inflammatory stimulation or intracellular bacterial infection. Notably, the small molecule MIF inhibitor 4-iodo-6-phenylpyrimidine inhibits MIF secretion by targeting the interaction between MIF and p115. These data reveal p115 to be a critical intermediary component in the regulated secretion of MIF from monocytes/macrophages.

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عنوان ژورنال:
  • Journal of immunology

دوره 182 11  شماره 

صفحات  -

تاریخ انتشار 2009