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

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 . 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 and . 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.