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

Authors
Yong, Ji InKim, Dae WonShin, Min JeaJo, Hyo SangPark, Jung HwanCho, Su BinLee, Chi HemYeo, Hyeon JiYeo, Eun JiChoi, Yeon JooKim, Ji AnHwang, Jung SoonKim, Duk-SooKim, Hyun AhCho, Yong-JunLee, Keun WookHan, Kyu HyungPark, JinseuEum, Won SikChoi, Soo Young
Issue Date
Nov-2018
Publisher
Elsevier BV
Keywords
PEP-1-PEA15; Inflammation; MAPK; Cytokines; Protein therapy
Citation
Immunobiology, v.223, no.11, pp 709 - 717
Pages
9
Journal Title
Immunobiology
Volume
223
Number
11
Start Page
709
End Page
717
URI
https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/5548
DOI
10.1016/j.imbio.2018.07.019
ISSN
0171-2985
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-1 beta, and TNF-alpha. 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.
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