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Tumour necrosis factor-α regulates human eosinophil apoptosis via ligation of TNF-receptor 1 and balance between NF-κB and AP-1

Kankaanranta, Hannu; Ilmarinen, Pinja; Zhang, Xianzhi; Adcock, Ian; Lahti, Aleksi; Barnes, Peter; Giembycz, Mark; Lindsay, Mark; Moilanen, Eeva (2014)

 
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Kankaanranta, Hannu
Ilmarinen, Pinja
Zhang, Xianzhi
Adcock, Ian
Lahti, Aleksi
Barnes, Peter
Giembycz, Mark
Lindsay, Mark
Moilanen, Eeva
2014

Plos ONE 9 2
1-11
Lääketieteen yksikkö - School of Medicine
This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
doi:10.1371/journal.pone.0090298
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201403121211

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Public Library of Science open access
Tiivistelmä
Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulatin​gfactor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, BMS-345541. TNF-α induced also an increase in AP-1 DNA-binding activity and the antiapoptotic effect of TNF-α was potentiated by inhibitors of AP-1, SR 11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase, SP600125, which is an upstream kinase activating AP-1. Our results thus suggest that TNF-α delays human eosinophil apoptosis via TNF-receptor 1 and the resulting changes in longevity depend on yin-yang balance between activation of NF-κB and AP-1.
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Kalevantie 5
PL 617
33014 Tampereen yliopisto
oa[@]tuni.fi | Tietosuoja | Saavutettavuusseloste