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三歧螺旋菌通过抑制中性粒细胞性哮喘中的 NLRP3 炎性小体发挥抗炎作用。

Anti-inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma.

机构信息

Department of Microbiology, Ajou University School of Medicine, Suwon, Republic of Korea.

Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea.

出版信息

J Cell Mol Med. 2024 Apr;28(8):e18356. doi: 10.1111/jcmm.18356.

DOI:10.1111/jcmm.18356
PMID:38668995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11048967/
Abstract

Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1β (IL-1β) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.

摘要

螺旋毛茛是一种一年生草本植物,属于菊科。螺旋毛茛提取物(TVE)具有抗疟原虫活性;然而,关于其抗炎作用及其分子机制尚未有详细报道。此外,草药植物通过抑制 NLRP3 炎性体发挥抗炎作用。因此,本研究的主要目的是通过测量白细胞介素-1β(IL-1β)的分泌来研究 TVE 对 NLRP3 炎性体激活的影响。我们用 TVE 处理脂多糖(LPS)诱导的 J774A.1 和 THP-1 细胞,发现 TVE 减弱了 NLRP3 炎性体的激活。值得注意的是,TVE 不影响核因子-κB(NF-κB)信号或细胞内活性氧(ROS)的产生和钾外流,这表明它通过其他机制使 NLRP3 炎性体失活。此外,TVE 抑制凋亡相关斑点样蛋白(ASC)斑和寡聚体的形成。免疫沉淀数据显示,TVE 减少了 NLRP3 与 NIMA 相关激酶 7(NEK7)的结合,从而减少了 ASC 寡聚体和斑的形成。此外,TVE 减轻了小鼠中性粒细胞性哮喘(NA)的症状。本研究表明,TVE 调节 NLRP3 与 NEK7 的结合,从而为 TVE 抑制 NLRP3 炎性体的机制提供了新的见解。这些发现表明 TVE 可能是 NLRP3 炎性体介导的疾病,特别是 NA 的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/dc23ce7dddca/JCMM-28-e18356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/fe6f9328b303/JCMM-28-e18356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/9e87980f4c49/JCMM-28-e18356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/79f5b8ceb70d/JCMM-28-e18356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/e35948f573ae/JCMM-28-e18356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/a5ce6a553236/JCMM-28-e18356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/dc23ce7dddca/JCMM-28-e18356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/fe6f9328b303/JCMM-28-e18356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/9e87980f4c49/JCMM-28-e18356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/79f5b8ceb70d/JCMM-28-e18356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/e35948f573ae/JCMM-28-e18356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/a5ce6a553236/JCMM-28-e18356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5a/11048967/dc23ce7dddca/JCMM-28-e18356-g005.jpg

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