Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression

Title
Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression
Author(s)
백석환임은정[임은정]박대원이진구이추희배외식[배외식]황영철[황영철]정재원[정재원]진병로
Keywords
CPG-B OLIGODEOXYNUCLEOTIDE; NF-KAPPA-B; TRANSCRIPTION FACTORS; CARDIAC MYOCYTES; CELL-SURVIVAL; GROWTH-FACTOR; TLR AGONISTS; ACTIVATION; PATHWAYS; DEATH
Issue Date
201008
Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE, v.42, no.10, pp.712 - 720
Abstract
Synthetic oligodeoxynucleotides (ODN) with a CpG-motif are recognized by Toll-like receptor 9 (TLR9) and pleiotropic immune responses are elicited. Stimulation of macrophages with TLR9 agonist prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). CpG ODN-mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway. Inhibition of TLR9 by small interfering (si) RNA or an inhibitor suppressed CpG ODN-mediated anti-apoptosis. Analysis of signaling pathways revealed that the anti-apoptotic effect of CpG ODN required phosphorylation of FoxO3a and its translocation from the nucleus to the cytosol. Overexpression of FoxO3a increased apoptosis induced by serum deprivation and CpG ODN blocked these effects through FLIP expression. In contrast, siRNA knock-down of FoxO3a decreased apoptosis by serum deprivation. In addition, Akt activation was involved in CpG ODN-induced phosphorylation of FoxO3a, expression of FLIP, and anti-apoptosis. Taken together, these results demonstrate the involvement of Akt-FoxO3a in TLR9-mediated anti-apoptosis and indicate that FoxO3a is a distinct regulator for FLIP expression.
URI
http://hdl.handle.net/YU.REPOSITORY/23867http://dx.doi.org/10.3858/emm.2010.42.10.070
ISSN
1226-3613
Appears in Collections:
의과대학 > 생화학.분자생물학교실 > Articles
의과대학 > 치과학교실 > Articles
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