Phosphatidylinositol 3-kinase modulates IL-18-induced nuclear factor-kappa B activation.
OBJECTIVE
To investigate whether phosphatidylinositol (PI) 3-kinase is involved in interleukin-18 (IL-18)-induced nuclear factor-kappa B (NF-kappa B) activation.


METHODS
Antisense PI 3-kinase oligonucleotide (ODN) was delivered by lipofectin encapsulation into cultured human hepatocellular carcinoma HepG2 cells. PI 3-kinase mRNA expression was assayed by semiquantitative reverse transcription-PCR. The levels of NF-kappa B were measured by sandwich ELISA.


RESULTS
(1) Antisense PI 3-kinase ODN blocked PI 3-kinase mRNA expression. (2) IL-18 activated NF-kappa B from basal level of 0.153 +/- 0.008 to 1.942 +/- 0.017. (3) Antisense PI 3-kinase ODN inhibited IL-18-induced NF-kappa B activation in a concentration (1-8 mg/L)- and time (5-24 h)-dependent fashion. When the cells were treated with antisense PI 3-kinase ODN 2 mg/L for 8 h, a maximum inhibitory rate was 35.2% from 1.942 +/- 0.017 control to 1.259 +/- 0.018.


CONCLUSIONS
PI 3-kinase is necessary for IL-18-stimulated NF-kappa B activation.
Guo
F K
FK
Institute of Pharmaceutic Sciences, First Military Medical University, Guangzhou 510515, China. jydyys@fimmu.edu.cn
Wu
S G
SG
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D006801:Humans; D020382:Interleukin-18 / Q000037:antagonists & inhibitors; D008113:Liver Neoplasms / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D020382:Interleukin-18; D016328:NF-kappa B; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases