Inhibition of AMP-activated protein kinase suppresses IL-2 expression through down-regulation of NF-AT and AP-1 activation in Jurkat T cells.
AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis and its activation during T cell receptor stimulation has recently been reported. In this study, we examined the role of AMPK in interleukin (IL)-2 production in T cells. Inhibition of AMPK by compound C, a specific inhibitor of AMPK or small interfering RNA of AMPKalpha1 suppressed IL-2 production in Jurkat T cells and peripheral blood lymphocytes stimulated with PMA plus ionomycin (PMA/Io) or with monoclonal anti-CD3 plus anti-CD28. We then showed that AMPK inhibition reduced PMA/Io-induced IL-2 mRNA expression and IL-2 promoter activation. Moreover, inhibition of AMPK suppressed transcriptional activation of NF-AT and AP-1, but not NF-kappaB, in PMA/Io-activated Jurkat cells. Finally, we found that compound C inhibited PMA/Io-induced phosphorylation of p38, JNK, and GSK-3beta but not of ERK. These results suggest that AMPK mediates IL-2 production by regulating NF-AT and AP-1activation during T cell stimulation.
Jhun
Bong Sook
BS
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. iskang@khu.ac.kr
Lee
Jung Yeon
JY
Oh
Young Taek
YT
Lee
Ju Hie
JH
Choe
Wonchae
W
Baik
Hyung Hwan
HH
Kim
Sung Soo
SS
Yoon
Kyung-Sik
KS
Ha
Joohun
J
Kang
Insug
I
D055372:AMP-Activated Protein Kinases; D015536:Down-Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000819:agonists / Q000378:metabolism*; D015533:Transcriptional Activation
D007376:Interleukin-2; D009097:Multienzyme Complexes; D050778:NFATC Transcription Factors; D018808:Transcription Factor AP-1; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases