BACKGROUND : It is well known that harmonious interactions among adhesion molecules and stromal cell-derived factor-1 (SDF-1)-mediated chemoattraction signalling via CXCR4 are needed for bone marrow homing of hematopoietic stem cells and progenitor cells. The aim of this study was to define the role of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta 1 (TFG-β₁), known as hematopoiesis-inhibitory cytokines, in the regulation of the molecules in relation to the homing.
METHODS : We investigated the effects of these cytokines on the expression of CXCR4 and adhesion molecules and the production of SDF-1 in bone marrow cells including CD34+ cells, bone marrow endothelial cells (BMEC-1 cells), and bone marrow stromal cells (BMSCs). We also examined whether the cytokines influence in vitro transmigration of hematopoietic progenitors.
RESULTS : None of the cytokines influenced CXCR4 expression on CD34+ cells or SDF-1-mediated chemotaxis of the cells. IFN-γ and TNF-α, but not TGF-β up-regulated the expression of L-selectin, ICAM-1, and VLA-4 on CD34+ cells. However, the up-regulation was not translated into the enhanced transendothelial migration. IFN-γ and TNF-α up-regulated the expression of VCAM-1 and ICAM-1 on BMEC-1 cells, and rendered the endothelium more suitable for transendothelial migration of hematopoietic progenitors. IFN-γ and TNF-α also up-regulated the expression of VCAM-1 and ICAM-1 on
primary human BMSCs. All three cytokines significantly attenuated SDF-1 production from primary BMSCs, and TNF-α diminished SDF-1 production from BMEC-1 cells.
CONCLUSION : These data indicate that IFN-γ, TNF-α, and TGF-β 1 play a role in the regulation of bone marrow homing of hematopoietic cells via up-regulation of adhesion molecule expression and down-modulation of SDF-1 production in bone marrow cells.

Keywords: Stromal cell-derived factor-1, CXCR4, adhesion molecules, interferon-gamma, tumor necrosis factor-α, transforming growth factor-β₁,