Format

Send to

Choose Destination
Immunobiology. 2018 Nov;223(11):709-717. doi: 10.1016/j.imbio.2018.07.019. Epub 2018 Jul 18.

PEP-1-PEA15 suppresses inflammatory responses by regulation of MAPK in macrophages and animal models.

Author information

1
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea.
2
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea.
3
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, Republic of Korea.
4
Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Kyunggi 14068, Republic of Korea.
5
Department of Neurosurgery, Hallym University Medical Center, Chuncheon 24253, Republic of Korea.
6
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: wseum@hallym.ac.kr.
7
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: sychoi@hallym.ac.kr.

Abstract

Phosphoprotein enriched in astrocytes 15 (PEA15) plays a multi-functional role in neuronal cell survival, however the effects of PEA15 against inflammation have not been investigated yet. To examine the effects of PEP-1-PEA15 protein against lipopolysaccharide (LPS)-induced inflammatory responses in Raw 264.7 cells and in a 12-O-tetradecanoylphobol 13-acetate (TPA)-induced mouse model, we constructed and purified PEP-1-PEA15 protein, which can transduce into cells or tissues. PEP-1-PEA15 inhibited LPS-induced damage in cells including that caused by reactive oxygen species (ROS) production and DNA fragmentation. PEP-1-PEA15 also significantly suppressed activation of mitogen activated protein kinases (MAPKs), pro-inflammatory mediator proteins and various cytokines. In a TPA-induced mouse ear edema model, PEP-1-PEA15 significantly reduced ear weight and thickness as well as MAPK activation as well as the expression levels of COX-2, iNOS, IL-6, IL-1β, and TNF-α. These results demonstrated that PEP-1-PEA15 showed anti-inflammatory effect in cells and animal model suggesting that this fusion protein protects cells or skin tissues from inflammatory response.

KEYWORDS:

Cytokines; Inflammation; MAPK; PEP-1-PEA15; Protein therapy

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center