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

Wisarut Payoungkiattikun,Nisachon Jangpromma,Boonpob Nowichai,Anupong Joompang,Sompong Klaynongsruang,Suyanee Thongchot

doi:10.1186/s13765-019-0488-3

Wisarut Payoungkiattikun, Nisachon Jangpromma + Show 4 more

Open Access

https://doi.org/10.1186/s13765-019-0488-3

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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.

Highlights

Bacterial infections are one of the main reasons for acute and chronic inflammation
Other studies indicated that some cationic peptides exhibit antimicrobial action and suppress the inflammation initiated by bacteria [23,24,25]
The primary results of this study demonstrated that KT2 and RT2 could suppress production levels of Nitric oxide (NO) (Fig. 1) and other inflammatory markers, including IL-1β, tumor necrosis factor-α (TNF-α), and IL-6, secreted from inflamed RAW 264.7 cells (Fig. 3) by forming a peptide-LPS complex that may obstruct the LPS-binding protein (Fig. 2)

Summary

Introduction

Bacterial infections are one of the main reasons for acute and chronic inflammation. In light of this knowledge, the endotoxin lipopolysaccharide (LPS), a constituent of Gram-negative bacterial outer membranes, acts as a key Payoungkiattikun et al Appl Biol Chem (2020) 63:5 promote the progress of various diseases and organ disorders [5,6,7,8,9].a connection between inflammation and oxidative stress has been proved. Bacterial infections are one of the main reasons for acute and chronic inflammation. In light of this knowledge, the endotoxin lipopolysaccharide (LPS), a constituent of Gram-negative bacterial outer membranes, acts as a key Payoungkiattikun et al Appl Biol Chem (2020) 63:5 promote the progress of various diseases and organ disorders [5,6,7,8,9]. Immoderate reactive oxygen species (ROS) generation is the key marker of oxidative stress occurrence. Verification indicates that this molecule is presented in various chronic inflammatory diseases [10]. The inhibition of the inflammation process might be an effective way to reduce cell damage from oxidative stress, the apoptosis process, and cancer development as well (Additional file 1: Fig. S1)

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Conclusion