Tumour necrosis factor-α regulates human eosinophil apoptosis via ligation of TNF-receptor 1 and balance between NF-κB and AP-1.
Tumour necrosis factor-α regulates human eosinophil apoptosis via ligation of TNF-receptor 1 and balance between NF-κB and AP-1.
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DOI：
10.1371/journal.pone.0090298
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Moilanen E
中科院分区：
文献类型：
--
作者：
Kankaanranta H;Ilmarinen P;Zhang X;Adcock IM;Lahti A;Barnes PJ;Giembycz MA;Lindsay MA;Moilanen E
嗜酸性粒细胞在哮喘中起核心作用。本研究旨在探讨肿瘤坏死因子-α（TNF-α）对人嗜酸性粒细胞寿命的影响。流式细胞术、DNA片段化分析和形态学分析结果表明，TNF-α抑制嗜酸性粒细胞凋亡，而Fas抑制嗜酸性粒细胞凋亡。TNF-α对嗜酸性粒细胞凋亡的影响可被TNF-α中和抗体逆转。TNF-α的抗凋亡作用不是由于自分泌释放已知的延长生存期的细胞因子白细胞介素3和5或粒细胞-巨噬细胞集落刺激因子，因为它们的中和作用不影响TNF-α的作用。抗凋亡信号主要由TNF受体1介导。TNF-α可诱导IκB的磷酸化和降解以及NF-κB DNA结合活性的增加。NF-κB吡咯烷二硫代氨基甲酸酯和胶质毒素抑制剂以及IκB激酶抑制剂BMS-345541可逆转TNF-α的生存延长作用。TNF-α还诱导AP-1 DNA结合活性的增加，并且TNF-α的抗凋亡作用被AP-1抑制剂SR 11302和丹参酮IIA以及c-jun-N-末端激酶抑制剂SP 600125（其是激活AP-1的上游激酶）增强。因此，我们的研究结果表明，TNF-α通过TNF-受体1延迟人类嗜酸性粒细胞凋亡，由此产生的寿命变化取决于NF-κB和AP-1激活之间的阴阳平衡。
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-stimulating factor 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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影响因子：
3.6
作者：
Lahti, A;Jalonen, U;Moilanen, E
通讯作者：
Moilanen, E
DOI：
10.2174/1568010054526395
发表时间：
2005-08-01
期刊：
Current Drug Targets - Inflammation and Allergy
影响因子：
--
作者：
Kankaanranta, Hannu;Moilanen, Eeva;Zhang, Xianzhi
通讯作者：
Zhang, Xianzhi
DOI：
10.1016/j.jaci.2007.10.028
发表时间：
2008-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brightling C;Berry M;Amrani Y
通讯作者：
Amrani Y
影响因子：
64.8
作者：
De Smaele, E;Zazzeroni, F;Franzoso, G
通讯作者：
Franzoso, G
影响因子：
20.3
作者：
Druilhe, A;Cai, ZZ;Pretolani, M
通讯作者：
Pretolani, M