JNK selective inhibitor, IQ-1S, protects the mice against lipopolysaccharides-induced sepsis

Sepsis is a severe systemic inflammatory response induced by infection. Innate immunity recognizes pathogen components such as lipopolysaccharides (LPS), and mediates the polarization of immune cells and the release of cytokines. However, this process is also crucial for triggering sepsis and septic shock. To investigate the potential therapeutic function of 11H-indeno [1,2-b] quinoxalin-11-one oxime (IQ-1S) to sepsis, LPS plus D-galactosamine was used to establish a sepsis mouse model. Flow cytometry was performed to catalyze T cells and macrophages in mouse spleen. ELISA assay and qRT-PCR assay were performed to estimate the expression levels of cytokines and related genes including TNF-alpha, IL-6, IL-18, Nos2, Arg and Mrc. The protein levels of NF -KB, AP1, NF-Y, pJNK2, JNK2, p-p38, p38, p-IKB alpha, IKB alpha, p-IKK8 and IKK8 were evaluated by Western blot assay. IQ-1S treatment significantly reduced mortality and lung inflammation in sepsis mice. IQ-1S treatment decreased the levels of inflammatory cytokines in sepsis mice. Polarization of M1 macrophages was suppressed by IQ-1S in vitro. IQ-1S significantly inhibited the activation of the JNK signaling pathway and reduced the phosphorylation level of JNK2 in sepsis mice. IQ-1S protected the mice against LPS-induced sepsis through inhibiting JNK signaling pathway.

Automated summary

The study demonstrated that IQ-1S significantly reduced mortality and lung inflammation in sepsis mice by inhibiting inflammatory cytokine levels and suppressing M1 macrophage polarization. Furthermore, IQ-1S effectively inhibited the activation of the JNK signaling pathway and reduced the phosphorylation level of JNK2 in sepsis mice, ultimately protecting the mice against LPS-induced sepsis.