Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways. 2023

Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
Emergency and Trauma College, Hainan Medical University, Haikou, Hainan, China; Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, Hainan, China.

Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI.

UI MeSH Term Description Entries
D008297 Male Males
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D048670 MAP Kinase Kinase 4 A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress. JN Kinase Kinase,JNK Kinase,JNK-Activating Protein Kinase,JNKK1 Protein Kinase,Jun Amino-Terminal Kinase Kinase,MEK4 Protein Kinase,Mitogen-Activated Protein Kinase Kinase 4,SAP Kinase Kinase 1,SAP Kinase-Extracellular Signal-Regulated Kinase Kinase 1,SAPK-ERK Kinase 1,SEK1 Protein Kinase,Stress-Activated Protein Kinase Kinase 1,JNK Activating Protein Kinase,Jun Amino Terminal Kinase Kinase,Kinase, JNKK1 Protein,Mitogen Activated Protein Kinase Kinase 4,Protein Kinase, JNK-Activating,Protein Kinase, JNKK1,Protein Kinase, MEK4,Protein Kinase, SEK1,SAP Kinase Extracellular Signal Regulated Kinase Kinase 1,SAPK ERK Kinase 1,Stress Activated Protein Kinase Kinase 1
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2

Related Publications

Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
April 2017, Oncotarget,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
January 2024, Molecular biology reports,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
January 2020, Frontiers in pharmacology,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
January 2020, American journal of translational research,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
November 2022, International journal of molecular medicine,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
April 2017, International immunopharmacology,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
February 2019, International immunopharmacology,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
August 2018, International immunopharmacology,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
January 2024, PloS one,
Hong Zhang, and Jun Zeng, and Jiankang Li, and Huankai Gong, and Meiling Chen, and Quan Li, and Shengxing Liu, and Shanjun Luo, and Huanxiang Dong, and Yingke Xu, and Huanling Duan, and Ling Haung, and Chuanzhu Lv
May 2017, Biological & pharmaceutical bulletin,
Copied contents to your clipboard!