Cytokine gene expression in regenerating haematopoietic tissues of mice after cyclophosphamide treatment.
The goal of the study was to investigate changes in expression of selected growth factors tentatively involved in regeneration of haematopoietic tissues (bone marrow and spleen) following cyclophosphamide (CY) damage in the mouse. The bone marrow (BM) and spleen were examined separately, since the regenerating pattern for haematopoietic progenitor cells (HPC) markedly differs in these two haematopoietically active organs after CY. Cytokines assumed to have a stimulatory effect on HPC - stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (flt3-ligand), thrombopoietin (TPO), stromal cell-derived factor 1 (SDF-1), oncostatin M (OSM) -, a suppressive effect on HPC proliferation - macrophage inflammatory protein-1alpha (MIP-1alpha), transforming growth factor-beta1 (TGFbeta1), tumour necrosis factor-alpha (TNFalpha) - and to be involved in migration of HPC (SCF, flt3-ligand, MIP1alpha, SDF-1) were examined at the level of mRNA expression by means of real-time RT-PCR. The expression of a particular cytokine appears to be similar in both BM and spleen of untreated mice. CY administration changed the expression pattern of the studied genes in BM and spleen. In BM, the levels of mRNAs for SCF and SDF-1 were increased and that for TGFbeta1 decreased at time intervals at which HPC are known to proliferate intensively during BM regeneration. In contrast, stimulated proliferation of HPC in spleen was accompanied by increased expression of flt3-ligand and oncostatin M. Upon mobilization of HPC from BM into blood after CY, the expression of SCF, TPO, SDF-1 and TGFbeta1 tends to decrease in BM. Accumulation of HPC in spleen is accompanied by increased mRNA for flt3-ligand and OSM. Our findings demonstrate that different cytokines may be involved in the proliferation and mobilization/homing of HPC during recovery after CY damage in BM and spleen.
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Department of Pathophysiology, First Medical School, Charles University, Prague, Czech Republic. oskar.psenak@lf1.cuni.cz
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Sýkora
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Chang
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D000818:Animals; D001853:Bone Marrow / Q000737:chemistry / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics; D003520:Cyclophosphamide / Q000009:adverse effects*; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012038:Regeneration; D013154:Spleen / Q000737:chemistry / Q000502:physiology*; D019089:Stem Cell Factor / Q000235:genetics; D013926:Thrombopoietin / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D008565:Membrane Proteins; C508352:Osm protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D019089:Stem Cell Factor; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D053683:Oncostatin M; D003520:Cyclophosphamide; D013926:Thrombopoietin