Down-regulation of MAPK/NF-κB signaling underlies anti-inflammatory response induced by transduced PEP-1-Prx2 proteins in LPS-induced Raw 264.7 and TPA-induced mouse ear edema model

• Published in: International immunopharmacology 2014-12, Vol.23 (2), p.426-433
• Main Authors: Jeong, Hoon Jae, Park, Meeyoung, Kim, Dae Won, Ryu, Eun Ji, In Yong, Ji, Cha, Hyun Ju, Kim, Sang Jin, Yeo, Hyeon Ji, Jeong, Ji-Heon, Kim, Duk-Soo, Kim, Hyoung Chun, Shin, Eun Joo, Park, Eun Young, Park, Jong Hoon, Kwon, Hyeok Yil, Park, Jinseu, Eum, Won Sik, Choi, Soo Young
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cysteamine - analogs & derivatives; Cysteamine - metabolism; Cytokines; Ear - pathology; Edema - chemically induced; Edema - metabolism; Gene Expression Regulation - physiology; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Inflammation; Macrophages - metabolism; Male; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinase Kinases - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Nitric Oxide; Oxidative stress; PEP-1-Prx2; Peptides - genetics; Peptides - metabolism; Protein therapy; Pyridines - toxicity; Signal Transduction - physiology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2014.09.008

Excessive reactive oxygen species (ROS) production plays a crucial role in causing various diseases, including inflammatory disorders. The activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling is implicated in stimulating inflammatory response and cytokines. Peroxiredoxin 2 (Prx2) is a 2-cysteine (Cys) peroxiredoxin capable of removing endogenous hydrogen peroxide (H2O2). PEP-1 peptide, a protein transduction domain, consists of three domains which are used to transduce exogenous therapeutic proteins into cells. The correlation between effectively transduced PEP-1-Prx2 and ROS-mediated inflammatory response is not clear. In the present study, we investigated the protective effects of cell permeable PEP-1-Prx2 on oxidative stress-induced inflammatory activity in Raw 264.7 cells and in a mouse ear edema model after exposure to lipopolysaccharides (LPS) or 12-O-tetradecanoylphorbol-13-acetate (TPA). Transduced PEP-1-Prx2 suppressed intracellular ROS accumulation and inhibited the activity of MAPKs and NF-κB signaling that led to the suppression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and cytokines in LPS-induced Raw 264.7 cells and TPA-induced mouse ear edema model. Given these results, we propose that PEP-1-Prx2 has therapeutic potential in the prevention of inflammatory disorders. •Transduced PEP-1-Prx2 ameliorates inflammatory response in LPS exposed cells.•PEP-1-Prx2 suppressed cellular ROS levels.•PEP-1-Prx2 inhibits MAPKs and NF-κB activation.•PEP-1-Prx2 inhibits inflammation response in vitro and in vivo.•PEP-1-Prx2 can be a therapeutic agent for disorders related to inflammation.