Cbf-14, a cationic peptide derived from cathelin-domain, exhibits anti-inflammation activity via inhibiting PI3K- Akt /ROS/ NF-κB signaling pathway

Abstract

Cbf-14 with the sequence RLLRKFFRKLKKSV, is an effective antimicrobial peptide derived from a cathelin-like domain. Previous reports have demonstrated that Cbf-14 not only exerts antimicrobial activity against penicillin-resistant bacteria but also alleviates bacterial-induced inflammation in E. coli BL21 (DE3)-NDM-1-infected mice. In this article, we demonstrated that Cbf-14 can effectively reduce RAW 264.7 intracellular infection caused by clinical strain E. coli and alleviate the inflammatory response of cells and improve cell survival after infection. Therefore, we established the LPS-stimulated RAW 264.7 cell inflammation model to uncover the molecular mechanisms of the peptide Cbf-14 in anti-inflammatory activity. The results reveal that Cbf-14 can decrease LPS-induced ROS secretion by blocking the membrane translocation of p47-phox subunits and suppressing p47-phox protein phosphorylation. Meanwhile, this peptide can down-regulate the over-expression of iNOS, and finally inhibit the NO excessive secretion from RAW 264.7 macrophages stimulated by LPS. Moreover, Cbf-14 also down-regulates the expression levels of p-IκB and p-p65 and inhibits the nuclear translocation of NF-κB through blocking MAPK- and/or PI3K-Akt signaling pathways. Overall, Cbf-14 exhibits anti-inflammatory activity through inhibiting NF-κB activity and ROS production via PI3K- Akt signaling pathway.