title: 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.
abstract: 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.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hoon Jae
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Meeyoung
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University , Gangneung 210-702, Republic of Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Ryu
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: In Yong
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyeon Ji
authors.initials: HJ
authors.lastname: Yeo
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, Republic of Korea.
authors.forename: Ji-Heon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, Republic of Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Hyoung Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyeok Yil
authors.initials: HY
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: wseum@hallym.ac.kr.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000378:metabolism; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000633:toxicity; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; D016328:NF-kappa B; C503924:Pep-1 peptide; D010455:Peptides; C115469:Prrx2 protein, mouse; D011725:Pyridines; C431843:tris(2-pyridylmethyl)amine; D009569:Nitric Oxide; D003543:Cysteamine; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Cytokines; Inflammation; Oxidative stress; PEP-1-Prx2; Protein therapy