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 .
- Author:
Deog Yeon JO
1
;
Jin Hee HWANG
;
Hyo Kyun CHUNG
;
Sang Eun PARK
;
Soo Jin PARK
;
Seung Keon KWAK
;
Hwan Jung YUN
;
Chu Myoung SEONG
;
Samyong KIM
Author Information
1. Department of Internal Medicine, Chungnam National University College of Medicine, Daejon, Korea. deogyeon@cuvic.cnu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Stromal cell-derived factor-1;
CXCR4;
adhesion molecules;
interferon-gamma;
tumor necrosis factor-alpha;
transforming growth factor-beta1
- MeSH:
Bone Marrow Cells*;
Bone Marrow*;
Chemotaxis;
Cytokines;
Endothelial Cells;
Endothelium;
Hematopoietic Stem Cells;
Humans*;
Integrin alpha4beta1;
Intercellular Adhesion Molecule-1;
Interferon-gamma*;
L-Selectin;
Mesenchymal Stromal Cells;
Stem Cells;
Transendothelial and Transepithelial Migration;
Transforming Growth Factor beta;
Transforming Growth Factor beta1;
Tumor Necrosis Factor-alpha*;
Up-Regulation;
Vascular Cell Adhesion Molecule-1
- From:Korean Journal of Hematology
2003;38(2):91-99
- CountryRepublic of Korea
- Language:Korean
-
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.
