[Intracellular localization of cycloferon, its binding with DNA and stimulation of cytokines expression after exposure to cycloferon].
Despite the wide usage of immunomodulating preparates including interferon inducers in medical practice little is known about their mechanism of action. We investigated some theoretical aspects of action of potent interferon inducer--cycloferon (10-carboxymethyl-9-acridanone), such as intracellular localization, ability to DNA binding and cytokine expression stimulation. This preparate has been found to be localized in nuclei of monocytic cells U-937, T- and B-lymphocytes and HeLa cells. In Hep-2 line cycloferon was bound to cells from non-adhesive subpopulation and was not detected in cells of monolayer. Human fibroblasts did not bind the substance. Interaction with double-stranded but not with single-stranded DNA occurred at pH lower than 4.7 regardless of the GC-contain. As shown by dot-hybridization cycloferon stimulated the transcription of interferon-alpha gene in U-937 cells 29-44-fold compared to the control but did not affect the transcription of tumor necrosis factor and interleukin-2 genes. Our data allow to propose that some specific receptor exists in cell with affinity to cycloferon.
Kovalenko
A L
AL
Institute of Cytology, Russian Academy of Sciences, St. Petersburg.
Kazakov
V I
VI
Slita
A V
AV
Zarubaev
V V
VV
Sukhinin
V P
VP
D000166:Acridines / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007369:Interferon Inducers / Q000378:metabolism* / Q000494:pharmacology; D016898:Interferon-alpha / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells
D000166:Acridines; D007369:Interferon Inducers; D016898:Interferon-alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; C026430:10-carboxymethyl-9-acridanone