PMID- 9172015 OWN - NLM STAT- MEDLINE DCOM- 19970818 LR - 20190909 IS - 0192-0561 (Print) IS - 0192-0561 (Linking) VI - 18 IP - 12 DP - 1996 Dec TI - (+/-)-3-[4-(2-dimethylamino-1-methylethoxy)-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. PG - 719-28 AB - (+/-)-3-[4-(2-Dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3, 4-b]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-25510 also stimulated the mRNA expression for IL-6 in both types of the cells, however, the stimulation required the presence of LPS. In THP-1 cells, the stimulation of IL-1 beta mRNA expression by Y-25510 was suppressed by cycloheximide, an inhibitor of protein synthesis. This phenomenon indicates that the stimulation requires de norv protein synthesis. In contrast, the stimulation of mRNA expression for IL-6 by Y-25510 was not suppressed by cycloheximide but suppressed by N alpha-p-tosyl-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 suppressed 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-25510 stimulates the mRNA expression for IL-1 beta and IL-6 by different mechanisms from those of LPS. FAU - Kusuhara, H AU - Kusuhara H AD - Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd, Fukuoka, Japan. FAU - Komatsu, H AU - Komatsu H FAU - Hisadome, M AU - Hisadome M FAU - Ikeda, Y AU - Ikeda Y LA - eng PT - Journal Article PL - England TA - Int J Immunopharmacol JT - International journal of immunopharmacology JID - 7904799 RN - 0 (Culture Media) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 0 (RNA, Messenger) RN - 145194-32-7 (Y 25510) RN - 402-71-1 (Tosylphenylalanyl Chloromethyl Ketone) RN - 7S5I7G3JQL (Dexamethasone) RN - 98600C0908 (Cycloheximide) SB - IM MH - Culture Media/metabolism/pharmacology MH - Cycloheximide/pharmacology MH - Dexamethasone/metabolism/pharmacology MH - Humans MH - Interleukin-1/*biosynthesis/genetics MH - Interleukin-6/*biosynthesis/genetics MH - Lipopolysaccharides/pharmacology MH - Monocytes/*metabolism MH - Pyrazoles/*pharmacology MH - Pyridines/*pharmacology MH - RNA, Messenger/*metabolism MH - Tosylphenylalanyl Chloromethyl Ketone/pharmacology MH - Tumor Cells, Cultured EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] AID - S0192056197855543 [pii] AID - 10.1016/s0192-0561(97)85554-3 [doi] PST - ppublish SO - Int J Immunopharmacol. 1996 Dec;18(12):719-28. doi: 10.1016/s0192-0561(97)85554-3.