Regulation of tumor necrosis factor gene expression in colorectal adenocarcinoma: in vivo analysis by in situ hybridization.

Leishmania donovani is an obligate intracellular protozoan which resides in macrophages and impairs a number of macrophage functions. We have undertaken to study this host cell-parasite interaction by examining the ability of L. donovani to impair the transmission of information from the cell surface to the nucleus and thus influence normal gene expression. We demonstrate that, in response to lipopolysaccharide, expression of both the c-fos and tumor necrosis factor genes was impaired in L. donovani-infected macrophages. Indomethacin reversed the parasite-mediated downregulation of the tumor necrosis factor gene but not the c-fos gene, suggesting that the impaired expression of these two genes occurred through different mechanisms. Direct stimulation of protein kinase C with oleoyl-2-acetoyl-3-glycerol did not abrogate inhibition of c-fos gene expression by L. donovani; however, L929 cell-conditioned medium induced a similar level of c-fos gene expression in both infected and noninfected macrophages. Impairment of c-fos gene expression by L. donovani thus appeared to be selective, depending on the external stimuli used to induce its expression. These data argue that L. donovani was capable of impairing macrophage gene expression in a selective rather than a general manner.

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Regulation of proto-oncogene and tumor necrosis factor gene expression by ethanol in HL-60 myeloid leukemia cells

Blood ◽

10.1182/blood.v76.2.298.298 ◽

1990 ◽

Vol 76 (2) ◽

pp. 298-301 ◽

Cited By ~ 24

Author(s):

R Datta ◽

ML Sherman ◽

DW Kufe

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Myeloid Leukemia ◽

Tumor Necrosis ◽

Terminal Differentiation ◽

Leukemia Cells ◽

Mrna Levels ◽

Factor Gene ◽

Tumor Necrosis Factor Gene ◽

Necrosis Factor

Abstract Previous studies have shown that certain low molecular weight polar solvents downregulate c-myc gene expression and induce terminal differentiation of human HL-60 myeloid leukemia cells. We have examined the effects of ethanol on gene expression in this cell line. The results show that while ethanol induces a more differentiated phenotype, this agent has little effect on the self-renewal capacity of HL-60 cells. Ethanol treatment was also associated with a concentration- dependent and transient downregulation of c-myc transcripts. Similar effects were observed for c-myb mRNA levels. The results further show that ethanol exposure is associated with induction of tumor necrosis factor gene expression. These findings indicate that ethanol induces changes in specific gene expression during non-terminal differentiation of HL-60 cells. The clinical effects of this agent could thus be related to altered patterns of gene expression in hematopoietic or other cells.

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c-fos and tumor necrosis factor gene expression in Leishmania donovani-infected macrophages.

Molecular and Cellular Biology ◽

10.1128/mcb.9.11.5223 ◽

1989 ◽

Vol 9 (11) ◽

pp. 5223-5227 ◽

Cited By ~ 59

Author(s):

A Descoteaux ◽

G Matlashewski

Keyword(s):

Gene Expression ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Leishmania Donovani ◽

L929 Cell ◽

Direct Stimulation ◽

Factor Gene ◽

Tumor Necrosis Factor Gene ◽

External Stimuli ◽

Necrosis Factor

Leishmania donovani is an obligate intracellular protozoan which resides in macrophages and impairs a number of macrophage functions. We have undertaken to study this host cell-parasite interaction by examining the ability of L. donovani to impair the transmission of information from the cell surface to the nucleus and thus influence normal gene expression. We demonstrate that, in response to lipopolysaccharide, expression of both the c-fos and tumor necrosis factor genes was impaired in L. donovani-infected macrophages. Indomethacin reversed the parasite-mediated downregulation of the tumor necrosis factor gene but not the c-fos gene, suggesting that the impaired expression of these two genes occurred through different mechanisms. Direct stimulation of protein kinase C with oleoyl-2-acetoyl-3-glycerol did not abrogate inhibition of c-fos gene expression by L. donovani; however, L929 cell-conditioned medium induced a similar level of c-fos gene expression in both infected and noninfected macrophages. Impairment of c-fos gene expression by L. donovani thus appeared to be selective, depending on the external stimuli used to induce its expression. These data argue that L. donovani was capable of impairing macrophage gene expression in a selective rather than a general manner.

Download Full-text