Original Research Article
Arecoline-induced death of human leukemia K562 cells is associated with surface up-modulation of TNFR2
Article first published online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 2240–2251, May 2012
How to Cite
Chen, Y.-J. and Chang, L.-S. (2012), Arecoline-induced death of human leukemia K562 cells is associated with surface up-modulation of TNFR2. J. Cell. Physiol., 227: 2240–2251. doi: 10.1002/jcp.22963
- Issue published online: 23 JAN 2012
- Article first published online: 23 JAN 2012
- Accepted manuscript online: 1 AUG 2011 08:41AM EST
- Manuscript Accepted: 22 JUL 2011
- Manuscript Received: 26 MAR 2011
- National Science Council, ROC. Grant Number: NSC98-2320-B110-002-MY3
The goal of the present study is to explore the contribution of tumor necrosis factor-α (TNFα)-related pathway to the cytotoxicity of arecoline on human leukemia K562 cells. Arecoline treatment induced death of K562 cells and increased surface expression of TNFα, TNFR1, and TNFR2. Unlike that of TNFR1 mRNA, transcriptional levels of TNFα and TNFR2 mRNA increased in arecoline-treated cells. Moreover, arecoline-induced down-regulation of ADAM17 maturation was involved in surface up-modulation of TNFR1, TNFR2, and TNFα. Arecoline-elicited increase in intracellular Ca2+ concentration was responsible for JNK/c-Jun pathway activation and ERK inactivation. Abolition of JNK/c-Jun pathway suppressed arecoline-induced increase in transcriptional level of TNFα and TNFR2 mRNA. TNFα and TNFR2 promoter luciferase activity and chromatin immunoprecipitating analyses revealed that c-Jun increasingly bound with TNFα and TNFR2 promoter upon arecoline treatment. Over-expression of constitutively active MEK1 abolished the effect of arecoline on suppressing ADAM17 maturation. Pretreatment with TNFR2 antibody abrogated arecoline-induced increased susceptibility of K562 cells for the cytotoxicity of TNFα and arecoline-induced cell death. Taken together, our data suggest that up-modulation of TNFR2 surface expression is associated with arecoline-induced death of K562 cells. J. Cell. Physiol. 227: 2240–2251, 2012. © 2011 Wiley Periodicals, Inc.