The Potential Role of Macrophage Migration Inhibitory Factor on the Migration of Vascular Smooth Muscle Cells

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  • Okamoto Toshiya
    Department of Medicine II, Hokkaido University Graduate School of Medicine.
  • Atsumi Toshiya
    Department of Medicine II, Hokkaido University Graduate School of Medicine.
  • Shimizu Chikara
    Department of Medicine II, Hokkaido University Graduate School of Medicine.
  • Yoshioka Narihito
    Department of Medicine II, Hokkaido University Graduate School of Medicine.
  • Koike Takao
    Department of Medicine II, Hokkaido University Graduate School of Medicine.

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Aim: Macrophage migration inhibitory factor (MIF) is known as a pro-inflammatory cytokine that regulates a broad spectrum of inflammatory reactions. MIF is expressed in vascular smooth muscle cells (VSMCs), and inhibition of the progression of atherosclerosis was observed in MIF-deficient atherosclerotic mice. However, the functional role of MIF in VSMCs has not been elucidated. The aim of this study was to investigate the role of MIF on the migration of VSMCs.<BR>Methods: Cultured rat A10 cells, derived from rat embryonic aortic smooth muscle cells, were stimulated with oxLDL, and the effect of MIF knockdown on oxLDL-mediated migration of A10 cells was analyzed.<BR>Results: Intracellular MIF content was significantly increased and a marked increase of MIF concent-ration was observed in the supernatant of A10 cells treated with oxLDL. The migration of A10 cells was significantly accelerated by the stimulation of recombinant MIF in a dose-dependent manner. Notably, knockdown of intracellular MIF by siRNA abolished oxLDL-induced migration of A10 cells.<BR>Conclusion: These findings suggest that MIF acts on the migration of VSMCs in an autocrine and paracrine fashion. MIF appears to be a novel target for the prevention of cardiovascular events.

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