肠道NF-κB通路介导的热致使肠内毒素引起的肠损伤有所增加
Xinrui Wang1, Wen Lu1, Ruibin Cai1
1Division of Emergency Medicine, Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China.
概括
热,一个关键的免疫反应,驱动肠道损伤在内毒性. 在肠道细胞中抑制NF-κB p65可降低 pyroptosis 和内 плазма网膜压力,改善存活率和肠道健康.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
背景情况:
- 热对于天生的免疫和病原体防御至关重要.
- 内毒素症会引发严重的炎症反应,但其对肠道细胞的影响尚不清楚.
- NF-κB信号传递与炎症过程有关.
研究的目的:
- 为了研究NF-κB p65介导的热中毒在内毒素引起的肠上皮细胞 (IEC) 损伤中的作用.
- 在这个过程中探索细胞内膜网膜 (ER) 压力的参与.
- 评估潜在的治疗策略,以向内毒性病的热化.
主要方法:
- 在IEC (p65IEC-KO) 和野生型 (WT) littermates 中使用了NF-κB p65删除的小鼠.
- 给药的脂多糖 (LPS) 诱导内毒性.
- 评估了肠道形态,烧亡标志物,透性,炎症,ER压力和生存率.
主要成果:
- 在WT小鼠的IEC中,LPS诱导了 pyroptosis,在p65IEC-KO小鼠中减少了.
- 内毒性导致肠损伤 (缩短小/密码,增加透性,炎症) 并减少了WT小鼠的存活率.
- 这些负面影响在p65IEC-KO小鼠中显著改善,低调ER压力.
结论:
- 通过NF-κB p65介导的热致使肠上皮细胞在内毒性病期间受损.
- ER压力是NF-κB驱动的热和随后的肠损伤的关键调解者.
- 向NF-κB介导的热和ER压力为内毒素引起的肠损伤提供了潜在的治疗途径.
相关概念视频
02:26NF-κB-dependent Signaling Pathway
7.9K
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...
7.9K
01:17The Extrinsic Apoptotic Pathway
6.6K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.6K
01:16Necrosis
4.9K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.9K
01:31The Intrinsic Apoptotic Pathway
6.9K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.9K
01:31Regulation of the Unfolded Protein Response
2.6K
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...
2.6K