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PLoS One. 2014 Jan 23;9(1):e86034. doi: 10.1371/journal.pone.0086034. eCollection 2014.

PEP-1-PON1 protein regulates inflammatory response in raw 264.7 macrophages and ameliorates inflammation in a TPA-induced animal model.

Author information

1
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Gangwondo, Korea.
2
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung, Gangwondo, Korea.
3
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, Chungcheonnamdo, Korea.
4
Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyongchon, Kyunggido, Korea.
5
Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.

Abstract

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.

PMID:
24465855
PMCID:
PMC3900452
DOI:
10.1371/journal.pone.0086034
[Indexed for MEDLINE]
Free PMC Article
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