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PMID:1845803

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Citation

Celada, A and Maki, RA (1991) IFN-gamma induces the expression of the genes for MHC class II I-A beta and tumor necrosis factor through a protein kinase C-independent pathway. J. Immunol. 146:114-20

Abstract

The mechanism of gene expression for the MHC I-A beta and TNF genes was studied in murine bone marrow macrophages. The treatment of macrophages with PMA stimulated the expression of TNF, but not I-A beta, suggesting that the TNF gene is responsive to activators of protein kinase C whereas the I-A beta gene is not. The treatment of macrophages with IFN-gamma led to an increase in the level of RNA for both TNF and I-A beta. The increase in expression of I-A beta and TNF, induced by IFN-gamma, was blocked by naphthalenesulfonamide or phenothiazine (trifluoperazine) but was not affected by the addition of isoquinolinesulfonamide or sphingosine. These results suggest that the induced expression of I-A beta and TNF by IFN-gamma is mediated by a pathway that is protein kinase C independent. This was supported by the finding that calcium ionophores were also able to induce the gene expression of both TNF and I-A beta. We observed that when both IFN-gamma and PMA were added to the macrophages, the level of RNA for TNF increased to a higher level than the level seen when either agent alone was added to the cells. In contrast, the addition of both IFN-gamma and PMA to macrophages had an inhibitory effect on the expression of the I-A beta gene. These results further emphasize the complex nature of gene regulation during the activation of macrophages.

Links

PubMed

Keywords

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Bone Marrow Cells; Calcimycin/pharmacology; Calmodulin/antagonists & inhibitors; Gene Expression Regulation/drug effects; Histocompatibility Antigens Class II/genetics; Interferon-gamma/pharmacology; Ionomycin/pharmacology; Isoquinolines/pharmacology; Macrophages/physiology; Major Histocompatibility Complex; Mice; Mice, Inbred DBA; Piperazines/pharmacology; Protein Kinase C/antagonists & inhibitors; Protein Kinase C/physiology; RNA, Messenger/metabolism; Sphingosine/pharmacology; Sulfonamides/pharmacology; Tetradecanoylphorbol Acetate/pharmacology; Trifluoperazine/pharmacology; Tumor Necrosis Factor-alpha/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HB2A

involved_in

GO:0071346: cellular response to interferon-gamma

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFNG

involved_in

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IFNG

involved_in

GO:0045348: positive regulation of MHC class II biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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