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

• Published in: Blood Vol. 107; no. 6; pp. 2252 - 2261
• Main Authors: Amin, M. Asif, Haas, Christian S., Zhu, Kui, Mansfield, Pamela J., Kim, Michael J., Lackowski, Nicholas P., Koch, Alisa E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-03-2006; The Americain Society of Hematology; The American Society of Hematology
• Subjects: Biological and medical sciences; Cell physiology; Chemokines, Cytokines, and Interleukins; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Motility and taxis; Human; Endothelial cell; Vascular cell adhesion molecule 1; Monocyte; Intercellular adhesion molecule 1; Enzyme; Transferases; Cell adhesion molecule; Inflammation; HL60 cell line; 1-Phosphatidylinositol 3-kinase; Regulation(control); Signaling pathway; Migration inhibitory factor; Transcription factor NFκB; Recombinant protein; Protein-tyrosine kinase; Cell migration
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-05-2011

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.