(+ THOXY)-PHENYL]-1H-PYRAZOLO[3,4-B]PYRIDINE-1-ACETIC ACID (Y-25510) STIMULATES PRODUCTION OF IL-1-BETA AND IL-6 AT THE LEVEL OF MESSENGER-RNA EXPRESSION IN CULTURED HUMAN MONOCYTES/
H. Kusuhara et al., (+ THOXY)-PHENYL]-1H-PYRAZOLO[3,4-B]PYRIDINE-1-ACETIC ACID (Y-25510) STIMULATES PRODUCTION OF IL-1-BETA AND IL-6 AT THE LEVEL OF MESSENGER-RNA EXPRESSION IN CULTURED HUMAN MONOCYTES/, International journal of immunopharmacology, 18(12), 1996, pp. 719-728
imethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3, 4]pyridine-1-acetic
acid (Y-25510) stimulated the mRNA expression for interleukin-1 beta
(IL-1 beta), and enhanced the expression induced by lipopolysaccharide
(LPS) in cultured human peripheral blood mononuclear cells (PBMC) and
THP-1 cells, a cell-line derived from human monocytic leukemia. Y-255
10 also stimulated the mRNA expression for IL-6 in both types of the c
ells, however, the stimulation required the presence of LPS. In THP-1
cells, the stimulation of IL-1 beta mRNA expression by Y-25510 was sup
pressed by cycloheximide, an inhibitor of protein synthesis. This phen
omenon indicates that the stimulation requires de novo protein synthes
is. In contrast, the stimulation of mRNA expression for IL-6 by Y-2551
0 was not suppressed by cycloheximide but suppressed by N alpha-p-tosy
l-L-phenylalanine chloromethyl ketone (TPCK), an inhibitor of nuclear
transcription factor-kappa B (NF-kappa B) activation, in the presence
of LPS, suggesting that the stimulation requires NF-kappa activation.
These results demonstrate that Y-25510 stimulates the mRNA expression
for IL-1 beta and IL-6 by different mechanisms. Dexamethasone suppress
ed the LPS-induced expression of mRNA for IL-1 beta and IL-6 in THP-1
cells, whereas the drug never suppressed the mRNA expression for these
cytokines in the presence of Y-25510. The result indicates that Y-255
10 stimulates the mRNA expression for IL-1 beta and IL-6 by different
mechanisms from those of LPS. (C) 1997 International Society for Immun
opharmacology.