Anti-inflammatory effect of transduced PEP-1-Cyclophilin A in Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate-induced mice

Min Jung Lee, Dae Won Kim, Eun Jeong Sohn, Hoon Jae Jeong, Min Jea Shin, Hye Won Kang, Eun Hee Ahn, Soon Won Kwon, Young Nam Kim, Moo Ho Won, Joon Kim, Sung Woo Cho, Tae Cheon Kang, Kyu Hyung Han, Jinseu Park, Won Sik Eum, Soo Young Choi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Aims: Cyclophilin A (CypA) is an immunophilin that acts as a receptor for the immunosuppressant drug cyclosporine A (CsA). CypA has emerged as a potential drug target for several inflammatory diseases, although the details of its mechanism are unclear. We examined the protective effects of CypA on inflammation in Raw 264.7 cells and animal models. Main methods: A human CypA gene was fused with a protein transduction domain, PEP-1 peptide, to construct a cell permeable PEP-1-CypA protein. The protein expression level of cyclooxygenase-2 (COX-2) and cytokines was detected by Western blot, ELISA and mRNA level of COX-2 and cytokines were measured by RT-PCR. The nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) activation were analyzed by Western blot and electrophoretic mobility shift assay. Skin inflammation was detected with immunohistochemistry. Key findings: Transduced PEP-1-CypA protein markedly inhibited lipopolysaccharide- and 12-O-tetradecanoyl phorbol-13-acetate-induced expression levels of COX-2 as well as pro-inflammatory cytokine levels in vitro and in vivo. Furthermore, transduced PEP-1-CypA protein resulted in a significant reduction in the activation of NF-kB and MAPK. Significance: The results indicate that PEP-1-CypA inhibits inflammatory response cytokines and enzymes by blocking NF-kB and MAPK activation upon stimulation of inflammation in vitro and in vivo. PEP-1-CypA protein may potentially be used as a therapeutic agent against skin diseases-related inflammation.

Original languageEnglish
Pages (from-to)896-904
Number of pages9
JournalLife Sciences
Volume89
Issue number23-24
DOIs
Publication statusPublished - 2011 Dec 5

Keywords

  • Cyclophilin A
  • Inflammation
  • Mitogen-activated protein kinase
  • NF-kB
  • Protein therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Anti-inflammatory effect of transduced PEP-1-Cyclophilin A in Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate-induced mice'. Together they form a unique fingerprint.

Cite this