A Cell-penetrating Peptide Suppresses Inflammation by Inhibiting NF-κB Signaling

Abstract

Nuclear factor-κB (NF-κB) is a central regulator of immune response and a potential target for developing anti-inflammatory agents. Mechanistic studies suggest that compounds that directly inhibit NF-κB DNA binding may block inflammation and the associated tissue damage. Thus, we attempted to discover peptides that could interfere with NF-κB signaling based on a highly conserved DNA-binding domain found in all NF-κB members. One such small peptide, designated as anti-inflammatory peptide-6 (AIP6), was characterized in the current study. AIP6 directly interacted with p65 and displayed an intrinsic cell-penetrating property. This peptide demonstrated significant anti-inflammatory effects in vitro and in vivo. In vitro, AIP6 inhibited the DNA-binding and transcriptional activities of the p65 NF-κB subunit as well as the production of inflammatory mediators in macrophages upon stimulation. Local administration of AIP6 significantly inhibited inflammation induced by zymosan in mice. Collectively, our results suggest that AIP6 is a promising lead peptide for the development of specific NF-κB inhibitors as potential anti-inflammatory agents.

Cathelicidin-BF suppresses intestinal inflammation by inhibiting the nuclear factor-κB signaling pathway and enhancing the phagocytosis of immune cells via STAT-1 in weanling piglets

“…NF-κB is a central regulator of the immune response and is a potential target for the development of anti-inflammatory agents. For example, anti-inflammatory peptide-6 (AIP6) suppressed inflammation by inhibiting NF-κB signaling in mice [29]. Accordingly, we also found that C-BF also suppressed LPS-inducing inflammation by inhibiting the IκB-α-NF-κB signaling pathway in porcine macrophages in vitro.…”

A Dual AP-1 and SMAD Decoy ODN Suppresses Tissue Fibrosis and Scarring in Mice

“…Cell proliferation was assessed by cell counting and [3H]-thymidine incorporation assay. Apoptosis was analyzed by flow cytometry as previously described (Wang et al, 2011). Details are found in Supplementary Materials and Methods online.…”

The six amino acid antimicrobial peptide bLFcin6 penetrates cells and delivers siRNA

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