AMP-activated protein kinase mediates T cell activation-induced expression of FasL and COX-2 via protein kinase C theta-dependent pathway in human Jurkat T leukemia cells
- Authors
- Lee, Jung Yeon; Choi, A-Young; Oh, Young Taek; Choe, Wonchae; Yeo, Eui-Ju; Ha, Joohun; Kang, Insug
- Issue Date
- Jun-2012
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- AMP-activated protein kinase; Jurkat; Ionomycin; COX-2; FasL; Protein kinase C theta
- Citation
- CELLULAR SIGNALLING, v.24, no.6, pp.1195 - 1207
- Journal Title
- CELLULAR SIGNALLING
- Volume
- 24
- Number
- 6
- Start Page
- 1195
- End Page
- 1207
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16337
- DOI
- 10.1016/j.cellsig.2012.01.015
- ISSN
- 0898-6568
- Abstract
- AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis, is known to be activated during T cell activation. T cell activation by T cell receptor (TCR) engagement or its pharmacological mimics, PMA plus ionomycin (PMA/Io), induces immunomodulatory FasL and cyclooxygenase-2 (COX-2) expression. In this study, we examined the role and mechanisms of AMPK in PMA/Io-induced expression of FasL and COX-2 in Jurkat T human leukemic cells. Inhibition of AMPK by a pharmacological agent, compound C, or AMPK alpha 1 siRNA suppressed expression of FasL and COX-2 mRNAs and proteins in PMA/Io-activated Jurkat cells. It also reduced secretion of FasL protein and prostaglandin E2, a main product of COX-2, in Jurkat cells and peripheral blood lymphocytes activated with PMA/Io or monoclonal anti-CD3 plus anti-CD28. Consistently, inhibition of AMPK blocked promoter activities of FasL and COX-2 in activated Jurkat cells. As protein kinase C theta (PKC theta) is a central molecule for TCR signaling, we examined any possible cross-talk between AMPK and PKC theta in activated T cells. Of particular importance, we found that inhibition of AMPK blocked phosphorylation and activation of PKC theta, suggesting that AMPK is an upstream kinase of PKC theta. Moreover, we showed that AMPK was directly associated with PKC theta and phosphorylated Thr538 of PKC theta in PMA/Io-stimulated Jurkat cells. We also showed that inhibition of PKC theta by rottlerin or dominant negative PKC theta reduced AMPK-mediated transcriptional activation of NF-AT and AP-1 in activated Jurkat cells. Taken together, these results suggest that AMPK regulates expression of FasL and COX-2 via the PKC theta and NF-AT and AP-1 pathways in activated Jurkat cells. (c) 2012 Elsevier Inc. All rights reserved.
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