Evidence of multi-functional peptide activity: potential role of KT2 and RT2 for anti-inflammatory, anti-oxidative stress, and anti-apoptosis properties

Abstract

Although several explications of anti-inflammatory therapeutic substances for treating inflammatory-related diseases have been broadly discussed within the last few decades, peptide-based compounds display the potential to be novel inflammation treatment agents. Here, we evaluated the anti-inflammatory activity and other inflammation-associated activities, including anti-oxidative stress and anti-apoptosis properties, of the cationic peptides KT2 and RT2. Nitric oxide (NO) and other inflammatory markers were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells co-incubated with peptides. The levels of interrelated gene and protein expressions were quantified. Peptides formed complexes with LPS and displayed anti-inflammatory properties by reducing NO and pro-inflammatory cytokine production in inflamed RAW 264.7 cells. These peptides also exhibit a strong suppressive effect on mRNA expression levels of inducible nitric oxide synthase, tumor necrosis factor-α, signal transducer and activator of transcription 1, c-Jun N-terminal protein kinase (JNK)-1, nuclear factor kappa B (NF-κB), and p38 mitogen-activated protein kinase (MAPK), which affects the decay of phosphorylated JNK-1, p38 MAPK, and NF-κB p65 protein expression. Both peptides induce up-regulation of anti-inflammatory mRNA and protein expression levels of extracellular signal-regulated kinase and mRNA expression levels of MAPK phosphatase-1. Also, the production of reactive oxygen species was observed to be markedly reduced. Furthermore, peptides exhibited an anti-apoptotic property. To our knowledge, this is the first report of the multi-functional peptides KT2 and RT2 exerting broad biological activity related to anti-inflammatory effects. These peptides have potential for delivering a medical method for the handling of inflammation-related diseases.