Differential regulation of BIRC2 and BIRC3 expression by inflammatory cytokines and glucocorticoids in pulmonary epithelial cells.
Differential regulation of BIRC2 and BIRC3 expression by inflammatory cytokines and glucocorticoids in pulmonary epithelial cells.
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DOI：
10.1371/journal.pone.0286783
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
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含有凋亡重复序列的杆状病毒抑制因子（BIRC）基因BIRC 2和BIRC 3的作用可能包括向炎性转录因子核因子-κB（NF-κB）发出信号并保护细胞免于死亡。然而，每个BIRC的不同功能并没有得到很好的界定。鉴于上皮在屏障功能和宿主防御中的作用，BIRC 2和BIRC 3表达在肺上皮细胞系和原代人支气管上皮细胞（pHBEC）中表征，所述原代人支气管上皮细胞（pHBEC）在浸没培养（SC）中生长为未分化细胞或在气液界面（ALI）处生长为高度分化细胞。在A549细胞中，白细胞介素-1 β（IL-1B）和肿瘤坏死因子α（TNF）诱导BIRC 3 mRNA（~20-50倍），在6-24 h蛋白表达最大。在BEAS-2B和Calu-3细胞以及SC和ALI pHBEC中发生了类似的作用。BIRC 2蛋白在未刺激的细胞中容易检测到，但不受IL 1B或TNF的显著调节。糖皮质激素（地塞米松，布地奈德）适度增加BIRC 3的mRNA和蛋白，但对BIRC 2的表达几乎没有影响。在A549细胞中，IL 1B诱导的BIRC 3 mRNA不受糖皮质激素的影响，并与TNF+糖皮质激素显示超加和性。在SC和ALI pHBEC中，IL 1B加布地奈德诱导的BIRC 3的超加和性也很明显。使用A549细胞，IL 1 B和TNF诱导的BIRC 3表达以及较小程度上的BIRC 2表达通过NF-κB抑制而被阻止。糖皮质激素诱导的BIRC 3表达通过沉默和拮抗糖皮质激素受体来阻止。而TNF，而不是IL 1B，诱导基础BIRC 2和BIRC 3蛋白的降解，IL 1B和TNF诱导的BIRC 3蛋白保持稳定。细胞因子和糖皮质激素的差异调节显示BIRC 2蛋白表达与快速信号传导事件中的作用一致，而苦参碱诱导的BIRC 3可能在后期效应中更重要。虽然TNF诱导的两种BIRC的降解可能会限制它们的活性，但精氨酸增强的BIRC 3表达可能为其功能做好准备。最后，屏蔽糖皮质激素抑制，或进一步增强糖皮质激素，可能表明BIRC 3的关键保护作用。
Roles for the baculoviral inhibitor of apoptosis repeat-containing (BIRC) genes, BIRC2 and BIRC3, may include signaling to the inflammatory transcription factor, nuclear factor-κB (NF-κB) and protection from cell death. However, distinct functions for each BIRC are not well-delineated. Given roles for the epithelium in barrier function and host defence, BIRC2 and BIRC3 expression was characterized in pulmonary epithelial cell lines and primary human bronchial epithelial cells (pHBECs) grown as undifferentiated cells in submersion culture (SC) or as highly differentiated cells at air-liquid interface (ALI). In A549 cells, interleukin-1β (IL1B) and tumor necrosis factor α (TNF) induced BIRC3 mRNA (~20-50-fold), with maximal protein expression from 6–24 h. Similar effects occurred in BEAS-2B and Calu-3 cells, as well as SC and ALI pHBECs. BIRC2 protein was readily detected in unstimulated cells, but was not markedly modulated by IL1B or TNF. Glucocorticoids (dexamethasone, budesonide) modestly increased BIRC3 mRNA and protein, but showed little effect on BIRC2 expression. In A549 cells, BIRC3 mRNA induced by IL1B was unchanged by glucocorticoids and showed supra-additivity with TNF-plus-glucocorticoid. Supra-additivity was also evident for IL1B-plus-budesonide induced-BIRC3 in SC and ALI pHBECs. Using A549 cells, IL1B- and TNF-induced BIRC3 expression, and to a lesser extent, BIRC2, was prevented by NF-κB inhibition. Glucocorticoid-induced BIRC3 expression was prevented by silencing and antagonism of the glucocorticoid receptor. Whereas TNF, but not IL1B, induced degradation of basal BIRC2 and BIRC3 protein, IL1B- and TNF-induced BIRC3 protein remained stable. Differential regulation by cytokines and glucocorticoids shows BIRC2 protein expression to be consistent with roles in rapid signaling events, whereas cytokine-induced BIRC3 may be more important in later effects. While TNF-induced degradation of both BIRCs may restrict their activity, cytokine-enhanced BIRC3 expression could prime for its function. Finally, shielding from glucocorticoid repression, or further enhancement by glucocorticoid, may indicate a key protective role for BIRC3.
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影响因子：
32.4
作者：
Bertrand, Mathieu J. M.;Doiron, Karine;Saleh, Maya
通讯作者：
Saleh, Maya
影响因子：
4.1
作者：
BARRETT, AJ;KEMBHAVI, AA;HANADA, K
通讯作者：
HANADA, K
影响因子：
16
作者：
Bertrand, Mathieu J. M.;Milutinovic, Snezana;Barker, Philip A.
通讯作者：
Barker, Philip A.
影响因子：
3.1
作者：
Du L;Xu C;Zeng Z;Chen F;Tang K;Liang Y;Guo Y
通讯作者：
Guo Y
DOI：
10.1016/j.jbc.2021.100687
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Gerber AN;Newton R;Sasse SK
通讯作者：
Sasse SK