IκB-激酶的诱导基因表达 ε 取决于人类肺上皮细胞中的核因子-κB
Amandah Necker-Brown1, Cora Kooi1,2, Andrew J Thorne1
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
The Biochemical journal
|June 28, 2024
概括
炎症性细胞因子如IL-1β和TNFα通过NF-κB在呼吸道细胞中的IκB-激酶-ε (IKKε) 进行上调. 这种细胞因子诱导的IKKε表达可能会导致抗葡萄糖皮质激素的炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 已知IκB-激酶-ε (IKKε) 在病毒刺激后可诱导免疫调节基因.
- 它通过炎症性细胞因子的调节,特别是在呼吸道上皮细胞中,人们对其理解较少.
- 呼吸道上皮细胞对于应对空气中的刺激物和驱动炎症至关重要.
研究的目的:
- 研究气道上皮细胞中由促炎性细胞因子对IKKε的上调调节.
- 阐明分子机制,特别是NF-κB在细胞因子诱导IKKε表达中的作用.
- 探索IKKε调节在葡萄糖皮质激素耐药性背景下的影响.
主要方法:
- 在肺上皮细胞系 (A549,BEAS-2B) 和初级人类支气管上皮细胞中IKKε表达的表征.
- 用促炎性细胞因子 (IL-1β,TNFα) 治疗和IKKε表达的分析.
- 使用染色体免疫沉 (ChIP) 来识别IKKε位点 (IKBKE) 内的NF-κB亚单元p65结合位点的机制研究.
- 报告者基因测试评估NF-κB结合区域的功能活性.
- 分析RNA聚合酶2招募和葡萄糖皮质类药物的作用.
主要成果:
- IL-1β和TNFα显著上调了气道上皮细胞中的IKKε表达.
- NF-κB信号通路对于这种细胞因子诱导的IKKε表达是必不可少的.
- 奇普测定证实NF-κB p65对IKBKE基因的特定5'和内基区域的强大招募.
- 报告员测定表明IL-1β和TNFα诱导活性在这些NF-κB结合位点.
- 葡萄糖皮质体治疗只部分抑制了IKKε的表达,这表明它在抗葡萄糖皮质体炎症中的作用.
结论:
- 亲炎性细胞因子IL-1β和TNFα通过NF-κB依赖的机制诱导空气道上皮细胞中的IKKε表达.
- 在IKKε位点内的多个NF-κB结合点调节其表达.
- IKKε表达对葡萄糖皮质激素的部分耐药性表明它参与了抗葡萄糖皮质激素的呼吸道炎症疾病.
更多相关视频
10:57NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
Published on: January 12, 2020
10.5K
09:17Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
18.1K
相关概念视频
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
MAPK Signaling Cascades
5.4K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.4K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
