A Peptide Derived from IKK-Interacting Protein Attenuates NF-κB Activation and Inflammation

The I kappa B kinase (IKK) complex plays a vital role in regulating the NF-kappa B activation. Aberrant NF-kappa B activation is involved in various inflammatory diseases. Thus, targeting IKK activation is an ideal therapeutic strategy to cure and prevent inflammatory diseases related to NF-kappa B activation. In a previous study, we demonstrated that IKK-interacting protein (IKIP) inhibits the phosphorylation of IKK alpha/beta and the activation of NF-kappa B through disruption of the formation of IKK complex. In this study, we identified a 15-aa peptide derived from mouse IKIP (46-60 aa of IKIP), which specifically suppressed IKK activation and NF-kappa B targeted gene expression via disrupting the association of IKK beta and NEMO. Importantly, administration of the peptide reduced LPS-induced acute inflammation and attenuated Zymosan-induced acute arthritis in mice. These findings suggest that this IKIP peptide may be a promising therapeutic reagent in the prevention and treatment of inflammatory diseases.

Automated summary

A 15-aa peptide derived from mouse IKIP was found to specifically suppress IKK activation and NF-kappa B targeted gene expression by disrupting the association of IKK beta and NEMO, reducing acute inflammation and arthritis in mice. This suggests that the IKIP peptide may be a promising therapeutic agent for inflammatory diseases.