scholarly journals Tumor necrosis factor and immune interferon synergistically induce cytochrome b-245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells.

1989 ◽  
Vol 83 (5) ◽  
pp. 1570-1579 ◽  
Author(s):  
M A Cassatella ◽  
L Hartman ◽  
B Perussia ◽  
G Trinchieri
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Cytochrome B ◽  
Heavy Chain ◽  
Nicotinamide Adenine Dinucleotide ◽  
Tumor Necrosis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Necrosis Factor

scholarly journals HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons.

1994 ◽  
Vol 14 (2) ◽  
pp. 1322-1332 ◽  
Author(s):  
D R Johnson ◽  
J S Pober
Keyword(s):  
Heavy Chain ◽  
Tumor Necrosis ◽  
Hla Class I ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Ifn Gamma ◽  
Histocompatibility Complex ◽  
Nuclear Factors ◽  
Necrosis Factor

The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN-gamma increase major histocompatibility complex class I molecule expression. A greater than additive (i.e., synergistic) induction of class I heavy-chain mRNA is observed in HeLa cells treated with TNF in combination with either type of IFN. To define the cis-acting elements mediating cytokine synergy, the promoter of a human major histocompatibility complex class I heavy-chain gene (HLA-B7) was placed in front of a reporter gene and transfected into HeLa cells. Deletion analysis mapped the elements required for synergy to a 40-bp region containing a kappa B-like element, which is necessary for the response to TNF, and an interferon consensus sequence (ICS), which is necessary for the responses to IFNs. When the orientation of these elements was reversed or their normal 20-bp spacing was reduced by 5 or 10 bp, i.e., one half or one full turn of the DNA helix, essentially equivalent responses were obtained, suggesting that these parameters are not critical. In electromobility shift assays, a p50-containing NF-kappa B nuclear factor from TNF-treated cells binds kappa B-containing probes, and ISGF-2 from IFN-gamma-treated cells binds ICS-containing probes. A probe containing both the kappa B and ICS elements (kappa B-ICS) forms a novel complex with nuclear factors isolated from cells treated with both TNF and IFN-gamma; this complex also forms when nuclear factors from individually cytokine-treated cells are mixed in vitro. The natural variant ICS found in HLA-A responds to IFN-gamma and can mediate synergy with TNF. However, the variant kappa B found in HLA-C does not respond to TNF, nor can it mediate synergy between TNF and IFN-gamma. These observations suggest that synergy between TNF and IFNs in the induction of HLA class I gene expression results from the sum of individual interactions of cytokine-activated enhancer-binding factors with the transcription initiation complex.

scholarly journals Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma.

1988 ◽  
Vol 85 (14) ◽  
pp. 5215-5219 ◽  
Author(s):  
P. E. Newburger ◽  
R. A. Ezekowitz ◽  
C. Whitney ◽  
J. Wright ◽  
S. H. Orkin
Keyword(s):  
Gene Expression ◽  
Cytochrome B ◽  
Interferon Gamma ◽  
Heavy Chain ◽  
Chain Gene ◽  
Heavy Chain Gene

scholarly journals HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons

1994 ◽  
Vol 14 (2) ◽  
pp. 1322-1332
Author(s):  
D R Johnson ◽  
J S Pober
Keyword(s):  
Heavy Chain ◽  
Tumor Necrosis ◽  
Hla Class I ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Ifn Gamma ◽  
Histocompatibility Complex ◽  
Nuclear Factors ◽  
Necrosis Factor

The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN-gamma increase major histocompatibility complex class I molecule expression. A greater than additive (i.e., synergistic) induction of class I heavy-chain mRNA is observed in HeLa cells treated with TNF in combination with either type of IFN. To define the cis-acting elements mediating cytokine synergy, the promoter of a human major histocompatibility complex class I heavy-chain gene (HLA-B7) was placed in front of a reporter gene and transfected into HeLa cells. Deletion analysis mapped the elements required for synergy to a 40-bp region containing a kappa B-like element, which is necessary for the response to TNF, and an interferon consensus sequence (ICS), which is necessary for the responses to IFNs. When the orientation of these elements was reversed or their normal 20-bp spacing was reduced by 5 or 10 bp, i.e., one half or one full turn of the DNA helix, essentially equivalent responses were obtained, suggesting that these parameters are not critical. In electromobility shift assays, a p50-containing NF-kappa B nuclear factor from TNF-treated cells binds kappa B-containing probes, and ISGF-2 from IFN-gamma-treated cells binds ICS-containing probes. A probe containing both the kappa B and ICS elements (kappa B-ICS) forms a novel complex with nuclear factors isolated from cells treated with both TNF and IFN-gamma; this complex also forms when nuclear factors from individually cytokine-treated cells are mixed in vitro. The natural variant ICS found in HLA-A responds to IFN-gamma and can mediate synergy with TNF. However, the variant kappa B found in HLA-C does not respond to TNF, nor can it mediate synergy between TNF and IFN-gamma. These observations suggest that synergy between TNF and IFNs in the induction of HLA class I gene expression results from the sum of individual interactions of cytokine-activated enhancer-binding factors with the transcription initiation complex.

scholarly journals Major Histocompatibility Complex (MHC) Class I Gene Expression in Single Neurons of the Central Nervous System: Differential Regulation by Interferon (IFN)-γ and Tumor Necrosis Factor (TNF)-α

1997 ◽  
Vol 185 (2) ◽  
pp. 305-316 ◽  
Author(s):  
H. Neumann ◽  
H. Schmidt ◽  
A. Cavalié ◽  
D. Jenne ◽  
H. Wekerle
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Mhc Class I ◽  
Tumor Necrosis ◽  
Constitutive Expression ◽  
Class I ◽  
Chain Gene ◽  
Tnf Α ◽  
Ifn Γ ◽  
Necrosis Factor

This study examined the effect of the pro-inflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) on the induction of MHC class I–related genes in functionally mature brain neurons derived from cultures of dissociated rat hippocampal tissue. Patch clamp electrophysiology combined with single cell RT-PCR demonstrated that ∼50% of the untreated neurons contained mRNA for MHC class I heavy chains, while, with few exceptions, the cells failed to transcribe β2-microglobulin and TAP1/TAP2 gene transcripts. No constitutive expression of MHC class I protein was detectable by confocal laser microscopy on the surface of neurons. All neurons transcribed the α-chain of the interferon-type II receptor (binding IFN-γ) along with the p55 receptor for TNF-α. Sustained exposure to IFN-γ resulted in transcription of β2microglobulin and TAP1/TAP2 genes and MHC class I surface expression in a minor part of the neurons, but did not alter their electrophysiological activities as assessed by whole cell electrophysiology. Suppression of neuronal electric activity by the sodium channel blocker tetrodotoxin drastically increased to almost 100% IFN-γ-mediated induction of MHC class I chains, of both TAP transporters, and of membrane expression of MHC class I protein. The effect of tetrodotoxin is at least partly reverted by the neurotransmitter glutamate. In contrast to IFN-γ, treatment with TNF-α did neither upregulate TAP1/TAP2 nor β2microglobulin gene expression, but induced MHC class I heavy chain gene transcription in all neurons. Consequently, no MHC class I molecules were detectable on the membranes of TNF-α-treated neurons.

scholarly journals Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester.

1989 ◽  
Vol 9 (1) ◽  
pp. 252-258 ◽  
Author(s):  
J Horiguchi ◽  
D Spriggs ◽  
K Imamura ◽  
R Stone ◽  
R Luebbers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leukotriene B4 ◽  
Mrna Levels ◽  
Arachidonic Acid Release ◽  
Acid Release ◽  
Tnf Gene ◽  
Necrosis Factor

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.

Sign in / Sign up

Export Citation Format

Share Document