PEP-1-PON1 protein regulates inflammatory response in raw 264.7 macrophages and ameliorates inflammation in a TPA-induced animal model.
Paraoxonase 1 (PON1) is an antioxidant enzyme which plays a central role in various diseases. However, the mechanism and function of PON1 protein in inflammation are poorly understood. Since PON1 protein alone cannot be delivered into cells, we generated a cell permeable PEP-1-PON1 protein using protein transduction domains, and examined whether it can protect against cell death in lipopolysaccharide (LPS) or hydrogen peroxide (H2O2)-treated Raw 264.7 cells as well as mice with 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin inflammation. We demonstrated that PEP-1-PON1 protein transduced into Raw 264.7 cells and markedly protected against LPS or H2O2-induced cell death by inhibiting cellular reactive oxygen species (ROS) levels, the inflammatory mediator's expression, activation of mitogen-activated protein kinases (MAPKs) and cellular apoptosis. Furthermore, topically applied PEP-1-PON1 protein ameliorates TPA-treated mice skin inflammation via a reduction of inflammatory response. Our results indicate that PEP-1-PON1 protein plays a key role in inflammation and oxidative stress in vitro and in vivo. Therefore, we suggest that PEP-1-PON1 protein may provide a potential protein therapy against oxidative stress and inflammation.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Mi Jin
MJ
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Hoon Jae
HJ
Jeong
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung, Gangwondo, Korea.
Dae Won
DW
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Eun Jeong
EJ
Sohn
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Hyo Sang
HS
Jo
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheonnamdo, Korea.
Duk-Soo
DS
Kim
Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyongchon, Kyunggido, Korea.
Hyun Ah
HA
Kim
Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.
Eun Young
EY
Park
Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.
Jong Hoon
JH
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Ora
O
Son
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Kyu Hyung
KH
Han
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Jinseu
J
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Won Sik
WS
Eum
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
Soo Young
SY
Choi
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate; D015107:4-Butyrolactone