PMID- 30049418 OWN - NLM STAT- MEDLINE DCOM- 20190625 LR - 20191210 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 223 IP - 11 DP - 2018 Nov TI - PEP-1-PEA15 suppresses inflammatory responses by regulation of MAPK in macrophages and animal models. PG - 709-717 LID - S0171-2985(18)30062-7 [pii] LID - 10.1016/j.imbio.2018.07.019 [doi] AB - 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-1beta, 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. CI - Copyright (c) 2018 Elsevier GmbH. All rights reserved. FAU - Yong, Ji In AU - Yong JI AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Kim, Dae Won AU - Kim DW AD - Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea. FAU - Shin, Min Jea AU - Shin MJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Jo, Hyo Sang AU - Jo HS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Park, Jung Hwan AU - Park JH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Cho, Su Bin AU - Cho SB AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Lee, Chi Hern AU - Lee CH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Yeo, Hyeon Ji AU - Yeo HJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Yeo, Eun Ji AU - Yeo EJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Choi, Yeon Joo AU - Choi YJ AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Kim, Ji An AU - Kim JA AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Hwang, Jung Soon AU - Hwang JS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Kim, Duk-Soo AU - Kim DS AD - Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, Republic of Korea. FAU - Kim, Hyun Ah AU - Kim HA AD - Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Kyunggi 14068, Republic of Korea. FAU - Cho, Yong-Jun AU - Cho YJ AD - Department of Neurosurgery, Hallym University Medical Center, Chuncheon 24253, Republic of Korea. FAU - Lee, Keun Wook AU - Lee KW AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Han, Kyu Hyung AU - Han KH AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Park, Jinseu AU - Park J AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. FAU - Eum, Won Sik AU - Eum WS AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: wseum@hallym.ac.kr. FAU - Choi, Soo Young AU - Choi SY AD - Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: sychoi@hallym.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180718 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (PEA15 protein, human) RN - 0 (Pep-1 peptide) RN - 0 (Peptides) RN - 0 (Phosphoproteins) RN - 0 (Reactive Oxygen Species) RN - 5UX2SD1KE2 (Cysteamine) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Apoptosis Regulatory Proteins MH - Cysteamine/*analogs & derivatives/metabolism MH - Cytokines/metabolism MH - DNA Fragmentation MH - Disease Models, Animal MH - Edema/*immunology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Humans MH - Inflammation/*immunology MH - Inflammation Mediators/metabolism MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Lipopolysaccharides/immunology MH - Macrophages/*immunology MH - Male MH - Mice MH - Mice, Inbred ICR MH - Peptides/*metabolism MH - Phosphoproteins/*metabolism MH - RAW 264.7 Cells MH - Reactive Oxygen Species/metabolism MH - Signal Transduction MH - Tetradecanoylphorbol Acetate/immunology OTO - NOTNLM OT - Cytokines OT - Inflammation OT - MAPK OT - PEP-1-PEA15 OT - Protein therapy EDAT- 2018/07/28 06:00 MHDA- 2019/06/27 06:00 CRDT- 2018/07/28 06:00 PHST- 2018/04/29 00:00 [received] PHST- 2018/07/10 00:00 [revised] PHST- 2018/07/17 00:00 [accepted] PHST- 2018/07/28 06:00 [pubmed] PHST- 2019/06/27 06:00 [medline] PHST- 2018/07/28 06:00 [entrez] AID - S0171-2985(18)30062-7 [pii] AID - 10.1016/j.imbio.2018.07.019 [doi] PST - ppublish SO - Immunobiology. 2018 Nov;223(11):709-717. doi: 10.1016/j.imbio.2018.07.019. Epub 2018 Jul 18.