Interleukin-17D produced by alveolar epithelial type II cells alleviates LPS-induced acute lung injury via the Nrf2 pathway.

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Shuan Dong, Shasha Liu, Qiaoying Gao, Jia Shi, Kai Song, Ya Wu, Huayang Liu, Chenxu Guo, Yan Huang, Shihan du, Xiangyun Li, Lixiu Ge, Jianbo Yu
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引用次数: 0

Abstract

Background: Sepsis engenders an imbalance in the body's inflammatory response, with cytokines assuming a pivotal role in its progression. A relatively recent addition to the interleukin-17 family, denominated interleukin-17D (IL-17D), is notably abundant within pulmonary confines. Nevertheless, its implication in sepsis remains somewhat enigmatic. The present study endeavors to scrutinize the participation of IL-17D in sepsis-induced acute lung injury (ALI).

Methods: The levels of IL-17D in the serum and bronchoalveolar lavage fluid (BALF) of both healthy cohorts and septic patients were ascertained through an ELISA protocol. For the creation of a sepsis-induced ALI model, intraperitoneal lipopolysaccharide (LPS) injections were administered to male C57/BL6 mice. Subsequently, we examined the fluctuations and repercussions associated with IL-17D in sepsis-induced ALI, probing its interrelation with nuclear factor erythroid 2-related factor 2 (Nrf2), alveolar epithelial permeability, and heme oxygenase-1.

Results: IL-17D levels exhibited significant reduction both in the serum and BALF of septic patients (P<0.001). Similar observations manifested in mice subjected to LPS-induced acute lung injury (ALI) (P=0.002). Intraperitoneal administration of recombinant interleukin 17D protein (rIL-17D) prompted increased expression of claudin 18 and concomitant enhancement of alveolar epithelial permeability, thus, culminating in improved lung injury (P<0.001). Alveolar epithelial type II (ATII) cells were identified as the source of IL-17D, regulated by Nrf2. Furthermore, a deficiency in HO-1 yielded elevated IL-17D levels (P=0.004), albeit administration of rIL-17D ameliorated the exacerbated pulmonary damage resulting from HO-1 deficiency.

Conclusion: Nrf2 fosters IL-17D production within AT II cells, thereby conferring a protective role in sepsis-induced ALI.

肺泡上皮II型细胞产生的白细胞介素-17D通过Nrf2途径减轻LPS诱导的急性肺损伤。
背景:脓毒症导致身体炎症反应失衡,细胞因子在其进展中发挥着关键作用。白细胞介素17家族中一个相对较新的成员,命名为白细胞介蛋白17D(IL-17D),在肺部范围内含量显著丰富。然而,它在败血症中的含义仍然有些神秘。本研究旨在探讨IL-17D在脓毒症诱导的急性肺损伤(ALI)中的作用。方法:采用ELISA法测定健康人群和脓毒症患者血清和支气管肺泡灌洗液(BALF)中IL-17D的水平。为了建立败血症诱导的ALI模型,对雄性C57/BL6小鼠进行腹膜内脂多糖(LPS)注射。随后,我们检测了败血症诱导的ALI中与IL-17D相关的波动和影响,探讨了其与核因子红系2相关因子2(Nrf2)、肺泡上皮通透性,结果:脓毒症患者血清和BALF中IL-17D水平显著降低(P结论:Nrf2促进AT II细胞内IL-17D的产生,从而在脓毒症诱导的ALI中发挥保护作用。
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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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