JNK‑IN‑8 treatment alleviates lipopolysaccharide‑induced acute lung injury via suppression of inflammation and oxidative stress regulated by JNK/NF‑κB signaling.

Abstract

JNK serves critical roles in numerous types of inflammation- and oxidative stress-induced disease, including acute lung injury (ALI). JNK-IN-8 is the first irreversible JNK inhibitor that has been described. However, whether JNK-IN-8 can prevent lipopolysaccharide (LPS)-induced ALI by inhibiting JNK activation and its downstream signaling is poorly understood. The objective of the present study was to investigate the specific therapeutic effects of JNK-IN-8 on LPS-induced ALI and the molecular mechanisms involved. JNK-IN-8 attenuated myeloperoxidase activity, malondialdehyde and superoxide dismutase content and the lung wet/dry ratio, and improved the survival rate following lethal injection of LPS. Additionally, JNK-IN-8 decreased bronchoalveolar lavage fluid protein levels, lactate dehydrogenase activity, neutrophil infiltration and the number of macrophages (as demonstrated by flow cytometry), as well as the production of TNF-α, IL-6 and IL-1β (as evaluated via ELISA). In addition, reverse transcription-quantitative PCR and ELISA showed that JNK-IN-8 attenuated LPS-induced inflammatory cytokine production and oxidative stress in primary murine peritoneal macrophages and RAW264.7 cells in vitro. Furthermore, the present study demonstrated that the JNK/NF-κB signaling pathway was involved in the therapeutic effect of JNK-IN-8 against LPS-induced injury both in vivo and in vitro. In conclusion, these findings indicated that JNK-IN-8 had a therapeutic effect on LPS-induced ALI in mice. The mechanism may be associated with inhibition of the JNK/NF-κB signaling pathway. JNK-IN-8 may be a potential therapeutic agent for the treatment of ALI.