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外膜毒力因子及与细胞焦亡相关的NLRP3、ASC、半胱天冬酶-1、gasdermin D、白细胞介素-1β和白细胞介素-18在溃疡和胃炎发病机制中的作用测定

Determination of the Roles of Outer Membrane Virulence Factors and Pyroptosis-Associated NLRP3, ASC, Caspase-1, Gasdermin D, IL-1β, and IL-18 in Ulcer and Gastritis Pathogenesis.

作者信息

Buyukcolak-Cebeci Yaren, Timucin Emel, Akcelik-Deveci Sumeyye, Mansur-Ozen Nesteren, Aydinlar Tuana, Tiftikci Arzu, Oktem-Okullu Sinem

机构信息

Department of Medical Biotechnology, Institute of Health and Science, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey.

Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey.

出版信息

Biology (Basel). 2025 May 30;14(6):634. doi: 10.3390/biology14060634.

DOI:10.3390/biology14060634
PMID:40563885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12189653/
Abstract

BACKGROUND

This study aims to investigate the association between pyroptosis and the outer membrane virulence factor of in patients with gastritis and ulcers.

METHODS

DNA, RNA, and protein were extracted from a single tissue sample taken from the antrum region of the stomach of volunteer patients. The expression of bacterial outer membrane virulence genes was analyzed at the gene level, and the expression levels of key pyroptosis markers were compared between -infected and uninfected gastritis and ulcer patient groups.

RESULTS

infection induced significant alterations in the expression levels of pyroptosis markers, including , , caspase-1, GSDMD, IL-18, and IL-1β, indicating a strong association with gastritis and ulcer pathology. Statistically significant correlations were observed between elevated levels of these markers and the activation of caspase-1 across different patient cohorts, supporting effective detection of pyroptosis. Both pro and active forms of caspase-1, GSDMD, IL-18, and IL-1β were assessed, revealing pyroptotic activity in specific patient samples. The vacA m2 allele showed a distinct response in gastritis versus ulcer patients and was associated with increased GSDMD expression in ulcerative cases. Along with the gene, this allele appears to play a critical role in the interaction between virulence and host pyroptotic responses. A statistically significant negative association was identified between the presence of the gene and Gasdermin D expression (odds ratio = 0, < 0.01), suggesting that Gasdermin D was absent in all -positive samples.

CONCLUSION

This study provides novel insights into the interrelation between the virulence factors of and pyroptosis in gastritis and ulcer diseases. Our findings demonstrate that infection significantly alters the expression levels of pyroptosis markers, including , , caspase-1, GSDMD, IL-18, and IL-1β, in gastric tissues. Notably, the vacA m2 allele was associated with a differential response in expression among patients with gastritis and ulcers, correlating with increased GSDMD levels in ulcerative conditions. The presence of the gene is markedly associated with the lack of Gasdermin D activation, indicating a possible suppressive function or immune evasion tactic. These results underscore the critical role of virulence determinants in modulating pyroptosis and suggest that understanding this relationship may pave the way for developing targeted therapeutic strategies to mitigate -associated pathologies.

摘要

背景

本研究旨在调查胃炎和溃疡患者中细胞焦亡与[细菌名称]外膜毒力因子之间的关联。

方法

从志愿患者胃窦区域采集的单个组织样本中提取DNA、RNA和蛋白质。在基因水平分析细菌外膜毒力基因的表达,并比较[细菌名称]感染组和未感染的胃炎及溃疡患者组中关键细胞焦亡标志物的表达水平。

结果

[细菌名称]感染导致细胞焦亡标志物(包括[相关基因名称1]、[相关基因名称2]、半胱天冬酶 -1、Gasdermin D、白细胞介素 -18和白细胞介素 -1β)的表达水平发生显著变化,表明其与胃炎和溃疡病理密切相关。在不同患者队列中,这些标志物水平升高与半胱天冬酶 -1的激活之间存在统计学上的显著相关性,支持了细胞焦亡的有效检测。对半胱天冬酶 -1、Gasdermin D、白细胞介素 -18和白细胞介素 -1β的前体形式和活性形式均进行了评估,在特定患者样本中发现了细胞焦亡活性。vacA m2等位基因在胃炎患者与溃疡患者中表现出不同的反应,且在溃疡性病例中与Gasdermin D表达增加相关。与[相关基因名称]一起,该等位基因似乎在[细菌名称]毒力与宿主细胞焦亡反应之间的相互作用中起关键作用。在[相关基因名称]的存在与Gasdermin D表达之间发现了统计学上显著的负相关(优势比 = 0,P < 0.01),表明在所有[细菌名称]阳性样本中均不存在Gasdermin D。

结论

本研究为胃炎和溃疡疾病中[细菌名称]的毒力因子与细胞焦亡之间的相互关系提供了新的见解。我们的研究结果表明,[细菌名称]感染显著改变了胃组织中细胞焦亡标志物(包括[相关基因名称1]、[相关基因名称2]、半胱天冬酶 -1、Gasdermin D、白细胞介素 -18和白细胞介素 -1β)的表达水平。值得注意的是,vacA m2等位基因与胃炎和溃疡患者中[相关基因名称]表达的差异反应相关,在溃疡性情况下与Gasdermin D水平升高相关。[相关基因名称]的存在与Gasdermin D激活的缺乏显著相关,表明可能具有抑制功能或免疫逃避策略。这些结果强调了[细菌名称]毒力决定因素在调节细胞焦亡中的关键作用,并表明了解这种关系可能为开发减轻[细菌名称]相关病理的靶向治疗策略铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/64151377fc8a/biology-14-00634-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/3c518104db17/biology-14-00634-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/d160d397ae86/biology-14-00634-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/6a5ce5060213/biology-14-00634-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/64151377fc8a/biology-14-00634-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/3c518104db17/biology-14-00634-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/d160d397ae86/biology-14-00634-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/6a5ce5060213/biology-14-00634-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbd/12189653/64151377fc8a/biology-14-00634-g004a.jpg

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