Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells.
BACKGROUND: Despite several reports describing the HSP70-mediated cytoprotection against IL-1, the precise mechanism for this phenomenon remains to be determined. METHODS/PRINCIPAL FINDINGS: Here we used HeLa cells, a human epithelial carcinoma cell line, to evaluate the role of inducible HSP70 in r...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3503766?pdf=render |
id |
doaj-71c0644f39bd42f9ba9586591e5e750e |
---|---|
record_format |
Article |
spelling |
doaj-71c0644f39bd42f9ba9586591e5e750e2020-11-25T00:09:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5005910.1371/journal.pone.0050059Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells.Xiang CaoLing YueJiYun SongQiuyue WuNa LiLan LuoLei LanZhimin YinBACKGROUND: Despite several reports describing the HSP70-mediated cytoprotection against IL-1, the precise mechanism for this phenomenon remains to be determined. METHODS/PRINCIPAL FINDINGS: Here we used HeLa cells, a human epithelial carcinoma cell line, to evaluate the role of inducible HSP70 in response of IL-1β stimulation. We found that inducible HSP70 antagonized the cytotoxicity of IL-1β and improved the survival of HeLa cells. Further investigation demonstrated that increased expression level of inducible HSP70 reduced the complex of TAK1 and HSP90, and promoted the degradation of TAK1 protein via proteasome pathway. By overexpression and RNAi knockdown, we showed that inducible HSP70 modulated the NF-kB but not MAPKs signalings through influencing the stability of TAK1 protein in HeLa cells. Moreover, overexpression of HSP70 attenuated the production of iNOS upon IL-1β stimulation, validating that inducible HSP70 serves as a cytopretective factor to antagonize the cytocidal effects of IL-1β in HeLa cells. CONCLUSIONS/SIGNIFICANCE: Our observations provide evidence for a novel signaling mechanism involving HSP70, TAK1, and NF-κB in the response of IL-1β cytocidal effects. This research also provides insight into mechanisms by which HSP70 exerts its cytoprotective action upon toxic stimuli in tumor cells.http://europepmc.org/articles/PMC3503766?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiang Cao Ling Yue JiYun Song Qiuyue Wu Na Li Lan Luo Lei Lan Zhimin Yin |
spellingShingle |
Xiang Cao Ling Yue JiYun Song Qiuyue Wu Na Li Lan Luo Lei Lan Zhimin Yin Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells. PLoS ONE |
author_facet |
Xiang Cao Ling Yue JiYun Song Qiuyue Wu Na Li Lan Luo Lei Lan Zhimin Yin |
author_sort |
Xiang Cao |
title |
Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells. |
title_short |
Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells. |
title_full |
Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells. |
title_fullStr |
Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells. |
title_full_unstemmed |
Inducible HSP70 antagonizes IL-1β cytocidal effects through inhibiting NF-kB activation via destabilizing TAK1 in HeLa cells. |
title_sort |
inducible hsp70 antagonizes il-1β cytocidal effects through inhibiting nf-kb activation via destabilizing tak1 in hela cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
BACKGROUND: Despite several reports describing the HSP70-mediated cytoprotection against IL-1, the precise mechanism for this phenomenon remains to be determined. METHODS/PRINCIPAL FINDINGS: Here we used HeLa cells, a human epithelial carcinoma cell line, to evaluate the role of inducible HSP70 in response of IL-1β stimulation. We found that inducible HSP70 antagonized the cytotoxicity of IL-1β and improved the survival of HeLa cells. Further investigation demonstrated that increased expression level of inducible HSP70 reduced the complex of TAK1 and HSP90, and promoted the degradation of TAK1 protein via proteasome pathway. By overexpression and RNAi knockdown, we showed that inducible HSP70 modulated the NF-kB but not MAPKs signalings through influencing the stability of TAK1 protein in HeLa cells. Moreover, overexpression of HSP70 attenuated the production of iNOS upon IL-1β stimulation, validating that inducible HSP70 serves as a cytopretective factor to antagonize the cytocidal effects of IL-1β in HeLa cells. CONCLUSIONS/SIGNIFICANCE: Our observations provide evidence for a novel signaling mechanism involving HSP70, TAK1, and NF-κB in the response of IL-1β cytocidal effects. This research also provides insight into mechanisms by which HSP70 exerts its cytoprotective action upon toxic stimuli in tumor cells. |
url |
http://europepmc.org/articles/PMC3503766?pdf=render |
work_keys_str_mv |
AT xiangcao induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT lingyue induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT jiyunsong induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT qiuyuewu induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT nali induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT lanluo induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT leilan induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells AT zhiminyin induciblehsp70antagonizesil1bcytocidaleffectsthroughinhibitingnfkbactivationviadestabilizingtak1inhelacells |
_version_ |
1725412979986399232 |