16 May 2018 : Laboratory Research
Ripasudil Attenuates Lipopolysaccharide (LPS)-Mediated Apoptosis and Inflammation in Pulmonary Microvascular Endothelial Cells via ROCK2/eNOS Signaling
Jianxin Yang1ABCDEF, Feng Ruan1ABCDEFG*, Zhongjun Zheng1ACEFDOI: 10.12659/MSM.910184
Med Sci Monit 2018; 24: LBR3212-3219
Abstract
BACKGROUND: Microvascular endothelial inflammation and apoptosis are responsible for septic acute lung injury (ALI). Ripasudil is a novel Rho/Rho kinase (ROCK) inhibitor which shows therapeutic effects on several vascular diseases. The aim of this study was to investigate the protective effects and correlated molecular mechanisms of ripasudil on lipopolysaccharide- induced inflammation and apoptosis of pulmonary microvascular endothelial cells (PMVECs).
MATERIAL AND METHODS: Cultured PMVECs were exposed to lipopolysaccharide (LPS). Ripasudil at various concentrations was used to treat the cells. Several cells were also co-administrated with the endothelial nitric oxide synthase (eNOS) inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Cell viability was assessed by MTT assay. Terminal dUTP transferase nick-end labeling (TUNEL) assay was used to detect the apoptosis. The colorimetric method was used to measure the activity of eNOS and ROCK2. Protein phosphorylation and expression were assessed by Western blotting.
RESULTS: Ripasudil attenuated the LPS-induced inflammation and apoptosis in PMVECs, which was reversed by L-NAME. Ripasudil suppressed ROCK2 activity and further increased the eNOS activity. Ripasudil treatment increased the phosphorylation of eNOS, increased the expression level of Bcl2, and decreased the expression level of active caspase3 in LPS-treated PMVECs. Moreover, the ripasudil treatment also inhibited the nuclear translocation of NF-κB and further suppressed the levels of interleukin (IL) 6 and tumor necrosis factor (TNF) α. The co-treatment with L-NAME, however, impaired the anti-apoptotic and anti-inflammatory effects of ripasudil on PMVECs without affecting ROCK2.
CONCLUSIONS: The novel ROCK2 inhibitor ripasudil suppressed LPS-induced apoptosis and inflammation in PMVECs by regulating the ROCK2/eNOS signaling pathway.
Keywords: acute lung injury, rho-Associated Kinases
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Clinical Research
Predicting Cerebral Small Vessel Disease Burden Based on Thromboelastography in Patients with Acute Ischemi...Med Sci Monit In Press; DOI: 10.12659/MSM.946303
Clinical Research
Long-Term Outcomes of Implanon in Managing Adenomyosis: A 3-Year Prospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945972
Laboratory Research
Linear Dimensional Accuracy in Maxillomandibular Records: A Comparative Study of Scannable and Transparent ...Med Sci Monit In Press; DOI: 10.12659/MSM.947265
Clinical Research
Efficacy of King's Combined Uterine Suture in Managing Placenta Accreta: A Retrospective AnalysisMed Sci Monit In Press; DOI: 10.12659/MSM.945826
Most Viewed Current Articles
17 Jan 2024 : Review article 6,969,932
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,896
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,741
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 20,253
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912