Inhibition of LPS-induced cyclooxygenase 2 and nitric oxide production by transduced PEP-1-PTEN fusion protein in Raw 264.7 macrophage cells.
10.3858/emm.2008.40.6.629
- Author:
Sun Hwa LEE
1
;
Yeom Pyo LEE
;
So Young KIM
;
Min Seop JEONG
;
Min Jung LEE
;
Hye Won KANG
;
Hoon Jae JEONG
;
Dae Won KIM
;
Eun Joung SOHN
;
Sang Ho JANG
;
Yeon Hyang KIM
;
Hyung Joo KWON
;
Sung Woo CHO
;
Jinseu PARK
;
Won Sik EUM
;
Soo Young CHOI
Author Information
1. Department of Biomedical Science and Research Institute for Bioscience and Biotechnology,College of Medicine, Hallym University, Chunchon, Korea. sychoi@hallym.ac.kr, wseum@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cyclooxygenase 2;
inflammation;
lipopolysaccharides;
nitric oxide;
PTEN phosphohydrolase
- MeSH:
Animals;
Cell Line;
Cyclooxygenase 2/*metabolism;
Cysteamine/*analogs & derivatives;
Enzyme Activation;
Humans;
Lipopolysaccharides/*pharmacology;
Macrophages/*metabolism;
Mice;
NF-kappa B/metabolism;
Nitric Oxide/*biosynthesis;
Nitric Oxide Synthase Type II/metabolism;
PTEN Phosphohydrolase/*genetics;
Peptides/*genetics;
Recombinant Fusion Proteins/*biosynthesis/genetics;
Signal Transduction
- From:Experimental & Molecular Medicine
2008;40(6):629-638
- CountryRepublic of Korea
- Language:English
-
Abstract:
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor. Although it is well known to have various physiological roles in cancer, its inhibitory effect on inflammation remains poorly understood. In the present study, a human PTEN gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-PTEN fusion protein. The expressed and purified PEP-1-PTEN fusion protein were transduced efficiently into macrophage Raw 264.7 cells in a time- and dose- dependent manner when added exogenously in culture media. Once inside the cells, the transduced PEP-1-PTEN protein was stable for 24 h. Transduced PEP-1-PTEN fusion protein inhibited the LPS-induced cyclooxygenase 2 (COX-2) and iNOS expression levels in a dose-dependent manner. Furthermore, transduced PEP-1-PTEN fusion protein inhibited the activation of NF-kappa B induced by LPS. These results suggest that the PEP-1-PTEN fusion protein can be used in protein therapy for inflammatory disorders.
