Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFκB

DOI PDF 被引用文献4件
  • M. Asif Amin
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.
  • Christian S. Haas
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.
  • Kui Zhu
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.
  • Pamela J. Mansfield
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.
  • Michael J. Kim
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.
  • Nicholas P. Lackowski
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.
  • Alisa E. Koch
    From the Department of Medicine, University of Michigan Medical School, Ann Arbor; the Department of Medicine, Northwestern University Medical School, Chicago, IL; the Veterans Administration Chicago Health Care Medical Center, Lakeside Division, Chicago, IL; and the Veterans Administration, Ann Arbor, MI.

説明

<jats:title>Abstract</jats:title><jats:p>Cell adhesion molecules are critical in monocyte (MN) recruitment in immune-mediated and hematologic diseases. We investigated the novel role of recombinant human migration inhibitory factor (rhMIF) in up-regulating vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and their signaling pathways in human MNs. rhMIF-induced expression of VCAM-1 and ICAM-1 was significantly higher compared with nonstimulated MNs. rhMIF induced MN VCAM-1 and ICAM-1 expression in a concentration-dependent manner (P < .05). Antisense oligodeoxynucleotides (ODNs) and inhibitors of Src, PI3K, p38, and NFκB significantly reduced rhMIF-induced MN VCAM-1 and ICAM-1 expression (P < .05). However, Erk1/2 and Jak2 were not involved. Silencing RNA directed against MIF, and inhibitors of Src, PI3K, NFκB, anti–VCAM-1, and anti–ICAM-1 significantly inhibited rhMIF-induced adhesion of HL-60 cells to human dermal microvascular endothelial cells (HMVECs) or an endothelial cell line, HMEC-1, in cell adhesion assays, suggesting the functional significance of MIF-induced adhesion molecules (P < .05). rhMIF also activated MN phospho-Src, -Akt, and -NFκB in a time-dependent manner. rhMIF induced VCAM-1 and ICAM-1 up-regulation in 12 hours via Src, PI3K, and NFκB as shown by Western blotting and immunofluorescence. MIF and MIF-dependent signaling pathways may be a potential target for treating diseases characterized by up-regulation of cell adhesion molecules.</jats:p>

収録刊行物

  • Blood

    Blood 107 (6), 2252-2261, 2006-03-15

    American Society of Hematology

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