title: Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice.
abstract: Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E2 (PGE2) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Kangneung 210-702, Republic of Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Jo
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Ryu
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Ji In
authors.initials: JI
authors.lastname: Yong
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Hyeon Ji
authors.initials: HJ
authors.lastname: Yeo
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Jong Kyu
authors.initials: JK
authors.lastname: Youn
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Jae Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, Republic of Korea.
authors.forename: Ji-Heon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090, Republic of Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: wseum@hallym.ac.kr.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea. Electronic address: sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000429:Alcohol Oxidoreductases / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004431:Ear, External / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D015696:Gene Products, tat / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013347:Subcellular Fractions / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000893:Anti-Inflammatory Agents; D015696:Gene Products, tat; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000429:Alcohol Oxidoreductases; C531129:CBR1 protein, human; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate
keywords: Apoptosis; Oxidative stress; Protein therapy; Skin inflammation; Tat-CBR1