Prolonged high glucose suppresses phorbol 12-myristate 13-acetate and ionomycin-induced interleukin-2 mRNA expression in Jurkat cells.
BACKGROUND
The disturbance of immunological responses is a complication of diabetes mellitus.


RESULTS
We cultured Jurkat cells in 11.1 (normal) and 22.2 mmol/l (high) glucose for 12 weeks and stimulated them with 10 nmol/l phorbol 12-myristate 13-acetate (PMA) and 500 nmol/l ionomycin. RT-PCR revealed that induced interleukin (IL)-2 mRNA expression levels were suppressed in high glucose cultures compared to those in normal glucose. Promoter activities of IL-2, nuclear factor of activated T cells (NFAT), and activator protein-1 (AP-1), after 6 h stimulation with PMA and ionomycin, gradually decreased in high glucose cultures to approximately 20% of those in normal glucose at 12 weeks. The prolonged culture in high glucose increased inducible cAMP early repressor (ICER) II mRNA and protein levels, and overexpression of ICER II dose-dependently suppressed promoter activities of IL-2, NFAT, and AP-1. Moreover, ICER II mRNA expression was transiently induced by stimulation with PMA and ionomycin in normal glucose cultures; however, with high glucose, the induction disappeared.


CONCLUSIONS
These results indicate that ICER II protein accumulates during prolonged culture in high glucose and suppresses IL-2 mRNA expression in Jurkat cells.
Higai
Koji
K
Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University Miyama 2-2-1, Funabashi, Chiba 247-8510, Japan. koji@phar.toho-u.ac.jp
Tsukada
Masatoshi
M
Moriya
Yumiko
Y
Azuma
Yutaro
Y
Matsumoto
Kojiro
K
D051786:Cyclic AMP Response Element Modulator / Q000096:biosynthesis / Q000235:genetics; D005947:Glucose / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology*; D019169:Jurkat Cells; D050778:NFATC Transcription Factors / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics
D007376:Interleukin-2; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D051786:Cyclic AMP Response Element Modulator; D015759:Ionomycin; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate