Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoic acid (RA) and interferons (IFNs) are negative regulators of cell proliferation. In vitro and in vivo, their combination leads to a more potent growth inhibition. However, the molecular mechanisms by which RA and IFNs potentiate each other are not fully understood. As some IFN-induced gene products regulate cell growth and/or antiviral activity, we analysed the effects of RA on their expressions. RA increases the level of 2'5'oligoadenylate synthetase, p68 kinase, the promyelocytic leukemia protein (PML) and Sp100 in both HL-60 and WISH cells. Moreover, RA and IFN act cooperatively to increase the expression of these proteins. RA also inhibits vesicular stomatitis virus replication and induces a higher antiviral state and growth inhibition when combined with IFN. RA stimulates the IFN regulatory factor 1 (IRF-1) gene expression directly through the GAS motif and causes the induction and secretion of IFNalpha. Additional mechanisms could be involved as RA increases the level of signal transducing activators of transcription (STAT) proteins, and enhances the IFN-induced STAT activation, suggesting that cooperative effects by RA and IFN are mediated through multiple pathways.
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PMID:Retinoic acid enhances the expression of interferon-induced proteins: evidence for multiple mechanisms of action. 939 79

The interferon (IFN)-induced promyelocytic leukemia (PML) protein is specifically associated with nuclear bodies (NBs) whose functions are yet unknown. Two of the NB-associated proteins, PML and Sp100, are induced by IFN. Here we show that overexpression of PML and not Sp100 induces resistance to infections by vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus (an orthomyxovirus) but not by encephalomyocarditis virus (a picornavirus). Inhibition of viral multiplication was dependent on both the level of PML expression and the multiplicity of infection and reached 100-fold. PML was shown to interfere with VSV mRNA and protein synthesis. Compared to the IFN mediator MxA protein, PML had less powerful antiviral activity. While nuclear body localization of PML did not seem to be required for the antiviral effect, deletion of the PML coiled-coil domain completely abolished it. Taken together, these results suggest that PML can contribute to the antiviral state induced in IFN-treated cells.
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PMID:Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein. 944 98