AICAR suppresses IL-2 expression through inhibition of GSK-3 phosphorylation and NF-AT activation in Jurkat T cells

Sook Jhun Bong, Taek Oh Young, Yeon Lee Jung, Yoon Kong, Kyung Sik Yoon, Soo Kim Sung, Hwan Baik Hyung, Joohun Ha, Insug Kang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

We examined the effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), the dephosphorylated form of AICA ribotide (also termed "ZMP"), an intermediate of purine biosynthesis, on interleukin (IL)-2 production in T cells. AICAR inhibited IL-2 production in Jurkat T cells and peripheral blood lymphocytes activated with PMA plus ionomycin (PMA/Io) or with monoclonal anti-CD3 plus anti-CD28. Pretreatment with 5′-iodotubercidin, an adenosine kinase inhibitor, enhanced AICAR suppression of IL-2 production, suggesting that AICAR, not ZMP, is responsible for IL-2 suppression. We then showed that AICAR inhibited PMA/Io-induced IL-2 mRNA expression and IL-2 promoter activation. AICAR inhibited DNA binding and transcriptional activation of NF-AT and to a lesser extent AP-1, but not NF-κB, in PMA/Io-activated Jurkat cells. Finally, we found that AICAR inhibited PMA/Io-induced phosphorylation of GSK-3 but not phosphorylation of ERK1/2, p38, and JNK. These results suggest that AICAR exerts its immunosuppressive effect in activated Jurkat cells by inhibiting GSK-3 phosphorylation and NF-AT activation.

Original languageEnglish (US)
Pages (from-to)339-346
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume332
Issue number2
DOIs
StatePublished - Jul 1 2005
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the Korean Ministry of Health and Welfare (02-PJ1-PG10-20904-0001), Korea Science and Engineering Foundation (R13-2002-020-01001-001-0; R04-2004-000-10070-0), and Korea Research Foundation (KRF-2002-015-EP0040).

Keywords

  • AICAR
  • GSK-3
  • IL-2
  • Immunosuppression
  • Ionomycin
  • Jurkat T cells
  • NF-AT
  • PMA

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