scholarly journals Tubulointerstitial Macrophage Accumulation is Regulated by Sequentially Expressed Osteopontin and Macrophage Colony-Stimulating Factor: Implication for the Role of Atorvastatin

2006 ◽  
Vol 2006 ◽  
pp. 1-9 ◽  
Author(s):  
Shaojiang Tian ◽  
Guohua Ding ◽  
Ruhan Jia ◽  
Guili Chu
Keyword(s):  
Treatment Group ◽  
Time Course ◽  
Interstitial Fibrosis ◽  
Statin Treatment ◽  
Histological Evaluation ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Macrophage Accumulation

Infiltration and local proliferation are known factors that contribute to tubulointerstitial macrophage accumulation. This study explored the time course of these two contributors' roles as tubulointerstitial inflammation and fibrosis progressing, and evaluated the mechanisms of the protective effect of atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess macrophage accumulation in interstitium. Histological evaluation was performed to semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after UUO operation, OPN expression significantly increased and positively correlated with the number of the interstitial ED1+cells, while on day 10, M-CSF expression upregulated and correlated with interstitial ED1+cells. In atorvastatin treatment group, the increments of these two factors were attenuated significantly at the two time points, respectively. ED1+cell accumulation and fibrosis also ameliorated in the treatment group. For all the samples of UUO and treatment group on day 10, ED1+cells also correlated with interstitial fibrosis scores. The results suggest that OPN may induce the early macrophage/monocyte infiltration and M-CSF may play an important role in regulating macrophage accumulation in later stage of UUO nephropathy. Statin treatment decreases interstitial inflammation and fibrosis, and this renoprotective effect may be mediated by downregulating the expression of OPN and M-CSF.

scholarly journals Peptide growth factors stimulate macrophage colony-stimulating factor in murine stromal cells

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 103-109 ◽  
Author(s):  
SL Abboud ◽  
M Pinzani
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Growth Factor ◽  
Stromal Cells ◽  
Time Course ◽  
Tnf Alpha ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Bone marrow stromal cells influence hematopoiesis through cell-cell interaction and release of hematopoietic growth factors. Macrophage colony-stimulating factor (M-CSF) is constitutively produced by several murine and human stromal cell lines and is induced by inflammatory mediators such as interleukin-1 alpha or tumor necrosis factor-alpha (TNF-alpha) in a variety of mesenchymal cells. Other potentially important regulatory molecules such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), released by activated monocytes in response to inflammation, stimulate the growth of human stromal cells. However, the effect of these peptide mitogens on M-CSF expression in stromal cells has not been explored. In this study, we used TC-1 murine bone marrow-derived stromal cells that constitutively secrete M-CSF to determine the effect of PDGF and bFGF on cell proliferation and M-CSF gene expression. PDGF and bFGF, but not TNF- alpha, were potent mitogens for the TC-1 cells. Similar to mouse L cells, TC-1 murine stromal cells constitutively expressed two major mRNA transcripts of 4.4 and 2.2 kb that hybridized to a murine M-CSF cDNA. PDGF, bFGF, and TNF-alpha markedly stimulated the steady-state expression of M-CSF mRNA with different time-course kinetics. The increased expression of M-CSF mRNA was associated with enhanced secretion of M-CSF as determined by radioimmunoassay. These findings suggest that PDGF, bFGF, and TNF-alpha may regulate hematopoiesis indirectly through release of M-CSF by stromal cells and may modulate, at least in part, the hematopoietic response to inflammation.

scholarly journals Peptide growth factors stimulate macrophage colony-stimulating factor in murine stromal cells

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 103-109 ◽  
Author(s):  
SL Abboud ◽  
M Pinzani
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Growth Factor ◽  
Stromal Cells ◽  
Time Course ◽  
Tnf Alpha ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Bone marrow stromal cells influence hematopoiesis through cell-cell interaction and release of hematopoietic growth factors. Macrophage colony-stimulating factor (M-CSF) is constitutively produced by several murine and human stromal cell lines and is induced by inflammatory mediators such as interleukin-1 alpha or tumor necrosis factor-alpha (TNF-alpha) in a variety of mesenchymal cells. Other potentially important regulatory molecules such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), released by activated monocytes in response to inflammation, stimulate the growth of human stromal cells. However, the effect of these peptide mitogens on M-CSF expression in stromal cells has not been explored. In this study, we used TC-1 murine bone marrow-derived stromal cells that constitutively secrete M-CSF to determine the effect of PDGF and bFGF on cell proliferation and M-CSF gene expression. PDGF and bFGF, but not TNF- alpha, were potent mitogens for the TC-1 cells. Similar to mouse L cells, TC-1 murine stromal cells constitutively expressed two major mRNA transcripts of 4.4 and 2.2 kb that hybridized to a murine M-CSF cDNA. PDGF, bFGF, and TNF-alpha markedly stimulated the steady-state expression of M-CSF mRNA with different time-course kinetics. The increased expression of M-CSF mRNA was associated with enhanced secretion of M-CSF as determined by radioimmunoassay. These findings suggest that PDGF, bFGF, and TNF-alpha may regulate hematopoiesis indirectly through release of M-CSF by stromal cells and may modulate, at least in part, the hematopoietic response to inflammation.

scholarly journals Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation.

1988 ◽  
Vol 168 (4) ◽  
pp. 1499-1504 ◽  
Author(s):  
G E Grau ◽  
V Kindler ◽  
P F Piguet ◽  
P H Lambert ◽  
P Vassalli
Keyword(s):  
T Lymphocytes ◽  
Cerebral Malaria ◽  
Colony Stimulating Factor ◽  
Experimental Cerebral Malaria ◽  
Neurological Syndrome ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Macrophage Accumulation

IL-3 and granulocyte/macrophage colony stimulating factor (GM-CSF) are two cytokines released by activated T lymphocytes that stimulate the growth and differentiation of various hematopoietic cell lines, among which are macrophages. It has been shown that TNF/cachectin, another cytokine that is released mostly by activated macrophages, plays a central role in experimental cerebral malaria (CM), an acute and lethal neurological syndrome induced by Plasmodium berghei ANKA infection in CBA mice. Since CM requires functional CD4+ T lymphocytes to occur, we explored, by injecting rabbit antibodies to murine rIL-3 and/or GM-CSF, whether these cytokines are intermediates in the marked TNF release leading to CM. Treatment of infected mice with each antibody separately had no protective effect. In contrast, when both anti-rGM-CSF and anti-rIL-3 antibodies were injected together; (a) the occurrence of neurological syndrome was prevented in 90% of the cases; (b) the rise in serum TNF was prevented; and (c) macrophage accumulation in the spleen was significantly reduced. Murine CM appears to involve a cytokine cascade in which IL-3 and GM-CSF lead to the accumulation of TNF-releasing macrophages in vivo.

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