Korean J Hematol.  2003 May;38(2):91-99.

Regulation of Adhesion Molecule Expression and Stromal Cell-Derived Factor-1 Production in Human Bone Marrow Cells by Interferon-gamma, Tumor Necrosis Factor-alpha, and Transforming Growth Factor-beta1: Implications in Bone Marrow Homing of Hematopoietic Cells

Affiliations
  • 1Department of Internal Medicine, Chungnam National University College of Medicine, Daejon, Korea. deogyeon@cuvic.cnu.ac.kr
  • 2Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.

Abstract

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-gamma), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TFG-beta1), 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-gamma and TNF-alpha, but not TGF-beta 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-gamma and TNF-alpha 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-gamma and TNF-alpha 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-alpha diminished SDF-1 production from BMEC-1 cells.
CONCLUSION
These data indicate that IFN-gamma, TNF-alpha, and TGF-beta1 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.

Keyword

Stromal cell-derived factor-1; CXCR4; adhesion molecules; interferon-gamma; tumor necrosis factor-alpha; transforming growth factor-beta1
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