Transduced PEP-1-FK506BP inhibits the inflammatory response in the Raw 264.7 cell and mouse models
- Authors
- Kim, So Young; Jeong, Hoon Jae; Kim, Dae Won; Kim, Mi Jin; An, Jae Jin; Sohn, Eun Jeong; Kang, Hye Won; Shin, Min Jea; Ahn, Eun Hee; Kwon, Soon Won; Kim, Duk-Soo; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young
- Issue Date
- Jul-2011
- Publisher
- Elsevier BV
- Keywords
- Cytokines; Inflammation; Mitogen-activated protein kinase; NF-kappa B; PEP-1-FK506BP; Protein therapy
- Citation
- Immunobiology, v.216, no.7, pp 771 - 781
- Pages
- 11
- Journal Title
- Immunobiology
- Volume
- 216
- Number
- 7
- Start Page
- 771
- End Page
- 781
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/16363
- DOI
- 10.1016/j.imbio.2010.12.008
- ISSN
- 0171-2985
- Abstract
- FK506 binding protein 12 (FK506BP) is an immunophilin that acts as a receptor for the immunosuppressant drug FK506. Although the precise action of FK506BP remains unclear, it has emerged as a potential drug target for several inflammatory diseases. This study investigated the protective effects of FK506BP on inflammation in vitro and in vivo using protein transduction. A cell-permeable expression vector PEP-1-FK506BP was constructed. Lipopolysaccharide (LPS)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated Raw 264.7 cells and ICR mice were treated with PEP-1-FK506BP. The expression of inflammatory response enzymes and cytokines was analyzed by Western blot, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay. PEP-1-FK506BP efficiently transduced into Raw 264.7 cells and markedly inhibited the expression levels of cyclooxygenase-2 as well as pro-inflammatory cytokines. Furthermore, transduced PEP-1-FK506BP significantly reduced activation of nuclear factor-kappa B (NF-kappa B) and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the cells, whereas PEP-1-FK506BP reduced phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in the animal models. These results indicate that PEP-1-FK506BP inhibits inflammatory response cytokines and enzymes by blocking NF-kappa B and MAPK including the phosphorylation of p38 and/or ERK MAPK in vitro and in vivo, suggesting that PEP-1-FK506BP may be a therapeutic agent against inflammatory skin diseases. (C) 2010 Elsevier GmbH. All rights reserved.
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Collections - College of Medicine > Department of Anatomy > 1. Journal Articles
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