Protective role of JNK inhibitor SP600125 in sepsis-induced acute lung injury.
Year: 2019
Type: article
Abstract: BACKGROUND: Whether the c-Jun N-terminal kinase (JNK) pathway mediates apoptosis in sepsis-induced acute lung injury is not known. Here we investigated the effect of JNK inhibition in a rat model of sepsis-induced lung injury, and assessed expression of JNK and endoplasmic reticulum stress-related proteins. METHODS: Sepsis was established by cecal ligation and puncture (CLP) in 48 male Sprague-Dawley rats. 32 additional rats underwent sham surgery. 24 CLP rats and 24 sham rats received tail vein injection of 30 mg/kg SP600125. The rest received saline injection. At 6, 12 and 24 h after surgery, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. p-JNK, XBP-1, ATF-4 and CHOP levels of the lung tissue were measured by western blot; and the JNK mRNA levels were measured by qPCR. RESULTS: The W/D ratios of lungs in the CLP group were significantly higher than those in the sham group, but lower those in the CLP+JNK inhibitor group (P<0.05). TUNEL staining revealed significantly more apoptotic cells in the lungs of the CLP group than the sham group, and in the CLP+JNK inhibitor group the apoptotic index was significantly reduced (P<0.05). XBP-1, ATF-4, CHOP and p-JNK protein levels and JNK mRNA levels were significantly elevated in the CLP group (P<0.05), but significantly ameliorated in the CLP+JNK inhibitor group (P<0.05). CONCLUSIONS: Inhibition of the JNK signaling pathway mitigates sepsis-induced lung injury. Our results suggest that JNK signaling promotes endoplasmic reticulum stress and thus apoptosis in sepsis-induced lung injury.
Source: Europe PMC (PubMed Central)
Authors: Liming Lou, Dandan Hu, Suzhen Chen, Shiqiang Wang, Yikai Xu, Yuenuo Huang, Yali Shi, Hong Zhang
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3008977274